U.S. patent application number 16/978435 was filed with the patent office on 2021-02-18 for emulsion composition.
This patent application is currently assigned to AstaReal Co., Ltd.. The applicant listed for this patent is AstaReal Co., Ltd.. Invention is credited to Rina Sakaguchi, Ryoji Sasaki, Kazuna Shitaka, Kumi Tominaga.
Application Number | 20210046006 16/978435 |
Document ID | / |
Family ID | 1000005222528 |
Filed Date | 2021-02-18 |
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United States Patent
Application |
20210046006 |
Kind Code |
A1 |
Shitaka; Kazuna ; et
al. |
February 18, 2021 |
EMULSION COMPOSITION
Abstract
Provided is an emulsion composition that is capable of enhancing
systemic absorption for various carotenoids, well compatible with
soft capsules, and capable of being formulated into a soft capsule
formulation, and that homogeneously disperses raw materials
including carotenoids and emulsifiers in the soft capsule
formulation. An emulsion composition containing a carotenoid, and
two or more specific emulsifiers selected from the group consisting
of tetraglycerin monooleate, decaglycerin monolaurate, sucrose
stearate, and sucrose laurate.
Inventors: |
Shitaka; Kazuna; (Toyama,
JP) ; Sasaki; Ryoji; (Toyama, JP) ; Sakaguchi;
Rina; (Toyama, JP) ; Tominaga; Kumi; (Toyama,
JP) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
AstaReal Co., Ltd. |
Toyama |
|
JP |
|
|
Assignee: |
AstaReal Co., Ltd.
Toyama
JP
|
Family ID: |
1000005222528 |
Appl. No.: |
16/978435 |
Filed: |
March 9, 2019 |
PCT Filed: |
March 9, 2019 |
PCT NO: |
PCT/JP2019/009549 |
371 Date: |
September 4, 2020 |
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61K 8/11 20130101; A61K
31/065 20130101; A61Q 19/02 20130101; A61K 47/14 20130101; A61K
8/60 20130101; A23L 33/15 20160801; A61K 9/4816 20130101; A61K
47/26 20130101; A61K 8/375 20130101; A23L 29/10 20160801; A61K
31/122 20130101; A61K 9/107 20130101; A23L 33/16 20160801; A61K
8/35 20130101; A23L 33/105 20160801; A23V 2002/00 20130101; A61Q
19/08 20130101; A61K 8/06 20130101 |
International
Class: |
A61K 9/107 20060101
A61K009/107; A61K 31/065 20060101 A61K031/065; A61K 31/122 20060101
A61K031/122; A61K 8/35 20060101 A61K008/35; A61K 8/11 20060101
A61K008/11; A61Q 19/08 20060101 A61Q019/08; A61Q 19/02 20060101
A61Q019/02; A61K 9/48 20060101 A61K009/48; A61K 8/06 20060101
A61K008/06; A61K 47/14 20060101 A61K047/14; A61K 8/37 20060101
A61K008/37; A61K 8/60 20060101 A61K008/60; A61K 47/26 20060101
A61K047/26; A23L 29/10 20060101 A23L029/10; A23L 33/105 20060101
A23L033/105; A23L 33/15 20060101 A23L033/15; A23L 33/16 20060101
A23L033/16 |
Foreign Application Data
Date |
Code |
Application Number |
Mar 9, 2018 |
JP |
2018-043661 |
Claims
1. An emulsion composition comprising a carotenoid and an
emulsifier, the emulsifier being any combination of the following
(a), (b), (c), (d), (e), (f), (g), (h), (i), and (j): (a)
tetraglycerin monooleate and decaglycerin monolaurate; (b)
tetraglycerin monooleate and sucrose stearate; (c) tetraglycerin
monooleate and sucrose laurate; (d) decaglycerin monolaurate and
sucrose laurate; (e) sucrose stearate and sucrose laurate; (f)
tetraglycerin monooleate, decaglycerin monolaurate, and sucrose
stearate; (g) tetraglycerin monooleate, decaglycerin monolaurate,
and sucrose laurate; (h) tetraglycerin monooleate, sucrose
stearate, and sucrose laurate; (i) decaglycerin monolaurate,
sucrose stearate, and sucrose laurate; and (j) tetraglycerin
monooleate, decaglycerin monolaurate, sucrose stearate, and sucrose
laurate.
2. An emulsion composition comprising a carotenoid, and
decaglycerin monolaurate and sucrose stearate, and being free of
lecithin.
3. The emulsion composition according to claim 1, further
comprising an alcohol.
4. The emulsion composition according to claim 1, wherein the
carotenoid is one or more selected from the group consisting of
lutein, zeaxanthin, astaxanthin, lycopene, .beta.-carotene,
.gamma.-carotene, phytofluene, phytoene, canthaxanthin,
.beta.-cryptoxanthin, capsanthin, fucoxanthin, and fatty acid
esters thereof.
5. The emulsion composition according to claim 4, wherein the
astaxanthin is derived from a Haematococcus algae extract.
6. The emulsion composition claim 1, further comprising a mineral,
or a vitamin or a combination thereof.
7. A soft capsule formulation comprising the emulsion composition
according to claim 1.
8. The emulsion composition according to claim 2, further
comprising an alcohol.
9. The emulsion composition according to claim 2, wherein the
carotenoid is one or more selected from the group consisting of
lutein, zeaxanthin, astaxanthin, lycopene, .beta.-carotene,
.gamma.-carotene, phytofluene, phytoene, canthaxanthin,
.beta.-cryptoxanthin, capsanthin, fucoxanthin, and fatty acid
esters thereof.
10. The emulsion composition according to claim 9, wherein the
astaxanthin is derived from a Haematococcus algae extract.
11. The emulsion composition claim 2, further comprising a mineral,
a vitamin or a combination thereof.
12. A soft capsule formulation comprising the emulsion composition
according to claim 2.
Description
TECHNICAL FIELD
[0001] The present invention relates to an emulsion composition,
specifically, an emulsion composition containing a carotenoid, and
two or more specific emulsifiers selected from the group consisting
of tetraglycerin monooleate, decaglycerin monolaurate (decaglyceryl
monolaurate), sucrose stearate, and sucrose laurate.
BACKGROUND ART
[0002] Most of poorly-soluble bioactive components handled in the
field of health foods, drugs, and quasi drugs suffer from problems
with systemic absorption. Carotenoids, which have recently been
attracting attention for the high functionality, are also
poorly-soluble bioactive components suffering from such problems
with systemic absorption, and typically handled in the form of an
emulsion composition to enhance the systemic absorption. Emulsion
compositions are classified into those of emulsified type formed by
adding water and an emulsifier to an oil component, and those of
self-emulsifying and pre-emulsified types formed by adding an
emulsifier to an oil component. Emulsion compositions of emulsified
type generally have a characteristic of quick dissolution in water,
and hence are used for beverages, cosmetics, and so on. Emulsion
compositions of self-emulsifying and pre-emulsified types are used
for soft capsule formulations, in which the blend ratio of water or
glycerin is limited.
[0003] Soft capsule formulations are formulations formed by
enclosing a drug, a supplement, or the like in powder, liquid, or
in another form in a capsule shell and molded, and this dosage form
is suitable for oral administration of bioactive components being
poorly-soluble, those having distinct odor or bitter taste, and
those being instable to oxygen or light. While such a component is
needed to be homogenously dispersed in a soft capsule formulation,
occasionally a raw material containing the component is unevenly
distributed in formulating into a soft capsule formulation. In
particular, when a powdery substance such as sucrose fatty acid
ester is used as a raw material, the raw material tends to be
dispersed in an inhomogeneous manner. On the other hands,
carotenoids are capable of being formulated into a soft capsule
formulation if being in an emulsion composition of self-emulsifying
or pre-emulsified type, but the systemic absorption is low.
Therefore, development of an emulsion composition of emulsified
type that is capable of being formulated into a soft capsule
formulation with high systemic absorption is demanded.
[0004] Emulsion compositions that enhance systemic absorption for
carotenoids and are capable of being formulated into a soft capsule
formulation were previously developed, and examples thereof include
a fat-reducing agent containing, as an active ingredient, a
carotenoid-containing composition containing a crystalline
carotenoid with 90% by mass thereof being amorphous, and a
(poly)glycerin fatty acid ester with the number of glycerin units
being 1 to 6 and the number of fatty acid units being 1 to 6,
wherein the (poly)glycerin fatty acid ester has at least one
hydroxy group in a glycerin unit (Patent Literature 1).
CITATION LIST
Patent Literature
[0005] Patent Literature 1: Japanese Patent Laid-Open No.
2012-206972
SUMMARY OF INVENTION
Technical Problem
[0006] However, the emulsion composition in Patent Literature 1 is
an emulsion composition that enhances systemic absorption only for
lycopene, one of carotenoids, and is capable of being formulated
into a soft capsule formulation, never an emulsion composition that
is capable of enhancing systemic absorption for various
carotenoids, and capable of being formulated into a soft capsule
formulation, thus having versatility for carotenoids.
[0007] The present invention was made to solve the above-described
problems, and an object of the present invention is to provide an
emulsion composition that is capable of enhancing systemic
absorption for various carotenoids, well compatible with soft
capsules, and capable of being formulated into a soft capsule
formulation, and that homogeneously disperses raw materials
including carotenoids and emulsifiers in the soft capsule
formulation.
Solution to Problem
[0008] The present inventors diligently studied to find that an
emulsion composition containing a carotenoid, and two or more
specific emulsifiers selected from the group consisting of
tetraglycerin monooleate, decaglycerin monolaurate, sucrose
stearate, and sucrose laurate is capable of enhancing systemic
absorption for various carotenoids, well compatible with soft
capsules, and capable of being formulated into a soft capsule
formulation, and homogeneously disperses raw materials including
carotenoids and emulsifiers in the soft capsule formulation, thus
completing the following invention.
[0009] (1) An emulsion composition containing a carotenoid and an
emulsifier, the emulsifier being any combination of the following
(a), (b), (c), (d), (e), (f), (g), (h), (i), and (j):
(a) tetraglycerin monooleate and decaglycerin monolaurate; (b)
tetraglycerin monooleate and sucrose stearate; (c) tetraglycerin
monooleate and sucrose laurate; (d) decaglycerin monolaurate and
sucrose laurate; (e) sucrose stearate and sucrose laurate; (f)
tetraglycerin monooleate, decaglycerin monolaurate, and sucrose
stearate; (g) tetraglycerin monooleate, decaglycerin monolaurate,
and sucrose laurate; (h) tetraglycerin monooleate, sucrose
stearate, and sucrose laurate; (i) decaglycerin monolaurate,
sucrose stearate, and sucrose laurate; and (j) tetraglycerin
monooleate, decaglycerin monolaurate, sucrose stearate, and sucrose
laurate.
[0010] (2) An emulsion composition containing a carotenoid, and
decaglycerin monolaurate and sucrose stearate, and being free of
lecithin.
[0011] (3) The emulsion composition according to (1) or (2),
containing an alcohol; here, examples of the alcohol can include,
but are not limited to, monohydric alcohols such as methanol and
ethanol, dihydric alcohols such as propylene glycol, and
(polyhydric) sugar alcohols such as xylitol, sorbitol, lactitol,
and erythritol.
[0012] (4) The emulsion composition according to any one of (1) to
(3), wherein the carotenoid is one or more selected from the group
consisting of lutein, zeaxanthin, astaxanthin, lycopene,
.beta.-carotene, .gamma.-carotene, phytofluene, phytoene,
canthaxanthin, .beta.-cryptoxanthin, capsanthin, fucoxanthin, and
fatty acid esters thereof.
[0013] (5) The emulsion composition according to (4), wherein the
astaxanthin is derived from a Haematococcus algae extract.
[0014] (6) The emulsion composition according to any one of (1) to
(5), containing a mineral and/or a vitamin.
[0015] (7) The emulsion composition according to any one of (1) to
(6), having a self-emulsifying property.
[0016] (8) A soft capsule formulation containing the emulsion
composition according to any one of (1) to (7).
[0017] (9) A method for producing the emulsion composition
according to (1), the method including the steps of:
[0018] preparing an aqueous phase by mixing and dissolving at least
sucrose stearate and/or sucrose laurate in water;
[0019] preparing an oil phase by mixing and dissolving at least a
carotenoid, and tetraglycerin monooleate and/or decaglycerin
monolaurate;
[0020] and subsequently mixing the aqueous phase and the oil phase
together to obtain an emulsion composition.
[0021] (10) A method for producing the emulsion composition
according to (1), the method including the steps of:
[0022] preparing an aqueous phase by mixing and dissolving at least
sucrose stearate in water;
[0023] preparing an oil phase by mixing and dissolving at least a
carotenoid, and one or more fatty acid esters selected from the
group consisting of sucrose laurate, tetraglycerin monooleate, and
decaglycerin monolaurate; and
[0024] subsequently mixing the aqueous phase and the oil phase
together to obtain an emulsion composition.
[0025] (11) A method for producing the emulsion composition
according to (1), the method including the steps of:
[0026] preparing an aqueous phase by mixing and dissolving at least
sucrose laurate in water;
[0027] preparing an oil phase by mixing and dissolving at least a
carotenoid, and one or more fatty acid esters selected from the
group consisting of sucrose stearate, tetraglycerin monooleate, and
decaglycerin monolaurate; and
[0028] subsequently mixing the aqueous phase and the oil phase
together to obtain an emulsion composition.
[0029] (12) A method for producing the emulsion composition
according to (1), the method including the steps of:
[0030] preparing an aqueous phase by mixing and dissolving at least
sucrose stearate and sucrose laurate in water;
[0031] preparing an oil phase by mixing and dissolving at least a
carotenoid and an oil or fat; and
[0032] subsequently mixing the aqueous phase and the oil phase
together to obtain an emulsion composition.
[0033] (13) A method for producing the emulsion composition
according to (1), the method including the steps of:
[0034] preparing an aqueous phase by mixing and dissolving a
water-soluble substance, as necessary, in water;
[0035] preparing an oil phase by mixing and dissolving at least a
carotenoid, and two or more fatty acid esters selected from the
group consisting of sucrose stearate, sucrose laurate,
tetraglycerin monooleate, and decaglycerin monolaurate; and
[0036] subsequently mixing the aqueous phase and the oil phase
together to obtain an emulsion composition.
[0037] (14) A method for producing the emulsion composition
according to (2), the method including the steps of:
[0038] preparing an aqueous phase by mixing and dissolving at least
sucrose stearate in water;
[0039] preparing an oil phase by mixing and dissolving at least a
carotenoid and decaglycerin monolaurate, without mixing and
dissolving lecithin; and
[0040] subsequently mixing the aqueous phase and the oil phase
together to obtain an emulsion composition.
[0041] (15) A method for producing the emulsion composition
according to (2), the method including the steps of:
[0042] preparing an aqueous phase by mixing and dissolving a
water-soluble substance, as necessary, in water;
[0043] preparing an oil phase by mixing and dissolving at least a
carotenoid, sucrose stearate, and decaglycerin monolaurate, without
mixing and dissolving lecithin; and
[0044] subsequently mixing the aqueous phase and the oil phase
together to obtain an emulsion composition.
[0045] (16) The method for producing an emulsion composition
according to any one of (9) to (15), the method including the step
of adding and mixing an alcohol in at least any step of the step of
preparing the aqueous phase, the step of preparing the oil phase,
the step of mixing the aqueous phase and the oil phase together,
and the step of mixing the water and the oil phase together.
[0046] (17) A method for producing a soft capsule formulation, the
method including the steps of:
[0047] preparing an aqueous phase by mixing and dissolving at least
sucrose stearate and/or sucrose laurate in water;
[0048] preparing an oil phase by mixing and dissolving at least a
carotenoid, and tetraglycerin monooleate and/or decaglycerin
monolaurate;
[0049] subsequently mixing the aqueous phase and the oil phase
together to obtain the emulsion composition according to (1);
and
[0050] subsequently enclosing a content containing the emulsion
composition in a soft capsule shell.
[0051] (18) A method for producing a soft capsule formulation, the
method including the steps of:
[0052] preparing an aqueous phase by mixing and dissolving at least
sucrose stearate in water;
[0053] preparing an oil phase by mixing and dissolving at least a
carotenoid, and one or more fatty acid esters selected from the
group consisting of sucrose laurate, tetraglycerin monooleate, and
decaglycerin monolaurate;
[0054] subsequently mixing the aqueous phase and the oil phase
together to obtain the emulsion composition according to (1);
and
[0055] subsequently enclosing a content containing the emulsion
composition in a soft capsule shell.
[0056] (19) A method for producing a soft capsule formulation, the
method including the steps of:
[0057] preparing an aqueous phase by mixing and dissolving at least
sucrose laurate in water;
[0058] preparing an oil phase by mixing and dissolving at least a
carotenoid, and one or more fatty acid esters selected from the
group consisting of sucrose stearate, tetraglycerin monooleate, and
decaglycerin monolaurate;
[0059] subsequently mixing the aqueous phase and the oil phase
together to obtain the emulsion composition according to (1);
and
[0060] subsequently enclosing a content containing the emulsion
composition in a soft capsule shell.
[0061] (20) A method for producing a soft capsule formulation, the
method including the steps of:
[0062] preparing an aqueous phase by mixing and dissolving at least
sucrose stearate and sucrose laurate in water;
[0063] preparing an oil phase by mixing and dissolving at least a
carotenoid and an oil or fat;
[0064] subsequently mixing the aqueous phase and the oil phase
together to obtain the emulsion composition according to (1);
and
[0065] subsequently enclosing a content containing the emulsion
composition in a soft capsule shell.
[0066] (21) A method for producing a soft capsule formulation, the
method including the steps of:
[0067] preparing an aqueous phase by mixing and dissolving a
water-soluble substance, as necessary, in water;
[0068] preparing an oil phase by mixing and dissolving at least a
carotenoid, and two or more fatty acid esters selected from the
group consisting of sucrose stearate, sucrose laurate,
tetraglycerin monooleate, and decaglycerin monolaurate;
[0069] subsequently mixing the aqueous phase and the oil phase
together to obtain the emulsion composition according to (1);
and
[0070] subsequently enclosing a content containing the emulsion
composition in a soft capsule shell.
[0071] (22) A method for producing a soft capsule formulation, the
method including the steps of:
[0072] preparing an aqueous phase by mixing and dissolving at least
sucrose stearate in water;
[0073] preparing an oil phase by mixing and dissolving at least a
carotenoid and decaglycerin monolaurate, without mixing and
dissolving lecithin;
[0074] subsequently mixing the aqueous phase and the oil phase
together to obtain the emulsion composition according to (2);
and
[0075] subsequently enclosing a content containing the emulsion
composition in a soft capsule shell.
[0076] (23) A method for producing a soft capsule formulation, the
method including the steps of:
[0077] preparing an aqueous phase by mixing and dissolving a
water-soluble substance, as necessary, in water;
[0078] preparing an oil phase by mixing and dissolving at least a
carotenoid, sucrose stearate, and decaglycerin monolaurate, without
mixing and dissolving lecithin;
[0079] subsequently mixing the aqueous phase and the oil phase
together to obtain the emulsion composition according to (2);
and
[0080] subsequently enclosing a content containing the emulsion
composition in a soft capsule shell.
[0081] (24) The method for producing a soft capsule formulation
according to any one of (17) to (23), the method including the step
of adding and mixing an alcohol in at least any step of the step of
preparing the aqueous phase, the step of preparing the oil phase,
the step of mixing the aqueous phase and the oil phase together,
and the step of mixing the water and the oil phase together.
[0082] (25) Use of a carotenoid and an emulsifier as an emulsion
composition, wherein the emulsifier is any combination of the
following (a), (b), (c), (d), (e), (f), (g), (h), (i), and (j):
(a) tetraglycerin monooleate and decaglycerin monolaurate; (b)
tetraglycerin monooleate and sucrose stearate; (c) tetraglycerin
monooleate and sucrose laurate; (d) decaglycerin monolaurate and
sucrose laurate; (e) sucrose stearate and sucrose laurate; (f)
tetraglycerin monooleate, decaglycerin monolaurate, and sucrose
stearate; (g) tetraglycerin monooleate, decaglycerin monolaurate,
and sucrose laurate; (h) tetraglycerin monooleate, sucrose
stearate, and sucrose laurate; (i) decaglycerin monolaurate,
sucrose stearate, and sucrose laurate; and (j) tetraglycerin
monooleate, decaglycerin monolaurate, sucrose stearate, and sucrose
laurate.
[0083] (26) Use of a carotenoid and an emulsifier containing
decaglycerin monolaurate and sucrose stearate as an emulsion
composition, wherein the emulsion composition is free of
lecithin.
[0084] (27) Use of an emulsion composition as a soft capsule
formulation, wherein the emulsion composition contains a carotenoid
and an emulsifier, the emulsifier being any combination of the
following (a), (b), (c), (d), (e), (f), (g), (h), (i), and (j):
(a) tetraglycerin monooleate and decaglycerin monolaurate; (b)
tetraglycerin monooleate and sucrose stearate; (c) tetraglycerin
monooleate and sucrose laurate; (d) decaglycerin monolaurate and
sucrose laurate; (e) sucrose stearate and sucrose laurate; (f)
tetraglycerin monooleate, decaglycerin monolaurate, and sucrose
stearate; (g) tetraglycerin monooleate, decaglycerin monolaurate,
and sucrose laurate; (h) tetraglycerin monooleate, sucrose
stearate, and sucrose laurate; (i) decaglycerin monolaurate,
sucrose stearate, and sucrose laurate; and (j) tetraglycerin
monooleate, decaglycerin monolaurate, sucrose stearate, and sucrose
laurate.
[0085] (28) Use of an emulsion composition as a soft capsule
formulation, wherein the emulsion composition contains a
carotenoid, and decaglycerin monolaurate and sucrose stearate, and
the emulsion composition is free of lecithin.
Advantageous Effects of Invention
[0086] The emulsion composition according to the present invention
is capable of enhancing systemic absorption for various
carotenoids, well compatible with soft capsules, and thus capable
of being formulated into a soft capsule formulation, and capable of
homogeneously dispersing raw materials including carotenoids and
emulsifiers in soft capsule formulations.
BRIEF DESCRIPTION OF DRAWINGS
[0087] FIG. 1 shows tables showing results of evaluation of
compatibility with a soft capsule (affinity with a soft capsule
shell) for emulsion compositions according to Examples 1 to 42.
[0088] FIG. 2 shows tables showing ratios of area under the blood
concentration-time curve (AUC.sub.0-24hr) between a comparative
composition and each of emulsion compositions according to Examples
1 to 42 for astaxanthin, lutein, and zeaxanthin.
[0089] FIG. 3 shows a table showing formulation and results of
evaluation of homogeneity for an emulsion composition according to
Example 11 with alcohol (ethanol) concentrations of 0% (0% by
weight), 0.1% (0.1% by weight), 0.25% (0.25% by weight), 0.5% (0.5%
by weight), 0.75% (0.75% by weight), and 1% (1% by weight).
[0090] FIG. 4 shows a table showing formulation and results of
evaluation of homogeneity for an emulsion composition according to
Example 34 with alcohol (ethanol) concentrations of 0% (0% by
weight), 0.1% (0.1% by weight), 0.25% (0.25% by weight), 0.5% (0.5%
by weight), 0.75% (0.75% by weight), and 1% (1% by weight).
[0091] FIG. 5 shows a table showing formulation and results of
evaluation of homogeneity for an emulsion composition according to
Example 36 with alcohol (ethanol) concentrations of 0% (0% by
weight), 0.1% (0.1% by weight), 0.25% (0.25% by weight), 0.5% (0.5%
by weight), 0.75% (0.75% by weight), and 1% (1% by weight).
[0092] FIG. 6 shows a table showing formulation and results of
evaluation of homogeneity for an emulsion composition according to
Example 36 with addition of any of propylene glycol (dihydric
alcohol), and (polyhydric) sugar alcohols including xylitol,
sorbitol, lactitol, and erythritol, in place of ethanol (monohydric
alcohol).
DESCRIPTION OF EMBODIMENTS
[0093] Hereinafter, an emulsion composition according to the
present invention and a production method therefor will be
described in detail. The emulsion composition according to the
present invention contains a carotenoid, and two or more specific
emulsifiers selected from the group consisting of tetraglycerin
monooleate, decaglycerin monolaurate (decaglyceryl monolaurate),
sucrose stearate, and sucrose laurate.
[0094] The carotenoid refers to a group of compounds classified as
one of terpenoids, and a collective term for aliphatic or alicyclic
polyenes including many conjugated double bonds as yellow or red
pigments (carotenoid pigments).
[0095] For the carotenoid applicable in the present invention, any
carotenoid may be selected without limitation, unless the
characteristics of the present invention are deteriorated, and
examples such carotenoids can include hydrocarbons (carotenes) and
oxidized alcohol derivatives thereof (xanthophylls), more
specifically, actinioerythrol, bixin, canthaxanthin, capsanthin,
capsorubin, .beta.-8'-apo-carotenal (apocarotenal),
.beta.-12'-apo-carotenal, .alpha.-carotene, .beta.-carotene,
carotene (a mixture of .alpha.- and .beta.-carotenes),
.gamma.-carotene, .beta.-cryptoxanthin, lutein, lycopene,
violerythrin, zeaxanthin, fucoxanthin, phytoene, phytofluene,
3,4,3',4'-tetradehydrolycopene, torulene, diaponeurosporene,
diapolycopene, diapolycopenedial, staphyloxanthin, crocetin,
adonirubin, adonixanthin, echinenone, asteroidenone, and
3-hydroxyechinenone. The scope of the carotenoid in the present
invention includes esters (fatty acid esters) and glycosides of
carotenoids including a hydroxy group or carboxy group among the
listed carotenoids. The carotenoid is not limited to
naturally-occurring carotenoids, and synthesized products of
carotenoids obtained in accordance with a conventional method are
also included in the scope of the carotenoid in the present
invention.
[0096] Among those carotenoids, one or more selected from the group
consisting of lutein, zeaxanthin, astaxanthin, lycopene,
.beta.-carotene, .gamma.-carotene, phytofluene, phytoene,
canthaxanthin, .beta.-cryptoxanthin, capsanthin, fucoxanthin, and
fatty acid esters of them are preferred, and one or more selected
from lutein, zeaxanthin, astaxanthin, and fatty acid esters of them
are more preferred.
[0097] Lutein (.beta.,.epsilon.-carotene-3,3'-diol) is known to be
rich in green and yellow vegetables such as spinach, kale, and
Japanese mustard spinach, and be rich, in the form of lutein fatty
acid ester, in fruits such as orange, peach, papaya, prune, and
mango, most flowers and vegetables, in particular, petals of
marigold. Lutein is abundant in the macula in the retina and
believed to function to exhibit protective action against light,
and reported to serve for prevention of age-related macular
degeneration, as well as protection of the macula. In addition,
lutein is confirmed to have effects of antioxidative activity such
as elimination activity for singlet oxygen, cancer prevention, and
so on.
[0098] For the lutein applicable in the present invention, any
lutein may be selected without limitation, unless the
characteristics of the present invention are deteriorated, and
examples of such lutein can include the above-described
naturally-occurring lutein from green and yellow vegetables,
flowers, vegetables, and so on, artificially produced lutein, and
lutein obtained through gene recombination. Commercially available
products of lutein may be used, and lutein in the form of a
pharmacologically acceptable salt may be used.
[0099] Zeaxanthin
(4-[18-(4-hydroxy-2,6,6-trimethyl-1-cyclohexenyl)-3,7,12,16-tetramethyl-o-
ctadeca-1,3,5,7,9,11,13,15,17-nonaenyl]-3,5,5-trimethyl-3-cyclohexen-1-ol)-
, a fat-soluble substance similar to .beta.-carotene, is a
structural isomer of lutein. As with the case of lutein, zeaxanthin
is abundant in the macular, and thus said to function to protect
the macular like lutein.
[0100] For the zeaxanthin applicable in the present invention, any
zeaxanthin may be selected without limitation, unless the
characteristics of the present invention are deteriorated, and
examples of such zeaxanthin can include naturally-occurring
zeaxanthin from plants such as corn, yolk, animal fat, and so on,
artificially produced zeaxanthin, and zeaxanthin obtained through
gene recombination. Commercially available products of zeaxanthin
may be used, and zeaxanthin in the form of a pharmacologically
acceptable salt may be used.
[0101] Astaxanthin
(3,3'-dihydroxy-.beta.,.beta.-carotene-4,4'-dione) is a red pigment
used for a wide variety of foods and widely distributed in the
nature, in particular, in oceans, and is derived from crustaceans
such as shrimps and crabs, fishes such as salmons and sea breams,
algae such as the green algae Haematococcus spp., yeasts such as
the red yeast Phaffia. Astaxanthin is known to have potent
antioxidative activity approximately 1000 times higher than that of
vitamin E and 40 times higher than that of .beta.-carotene, and
have bioactivities including antioxidative effect,
anti-inflammatory effect, antiaging effect for the skin, and
whitening effect. In addition, astaxanthin is known as a pigment in
the range of yellow to red. There are three isomers of astaxanthin,
the 3S,3'S-form, the 3S,3'R-form (meso-form), and the 3R,3'R-form,
which have different conformations of the hydroxy group at position
3(3') in the ring structure present at each end of the molecule.
Further, there are geometric isomers of astaxanthin due to
cis-/trans-configuration in conjugated double bonds in the center
of the molecule. For example, there are the all-trans-form, the
9-cis-form, and the 13-cis-form. Moreover, the hydroxy group at
position 3(3') is capable of forming an ester form with a fatty
acid.
[0102] Further, astaxanthin is known as a highly safe compound for
which no mutagenicity has been observed, and is widely used as a
food additive (Takahashi, Jiro et al.: Toxicity Test of
Haematococcus Algae Astaxanthin--Ames Test, Toxicity Test with
Single Administration to Rats, Toxicity Test with Repetitive Oral
Administration to Rats for 90 Days --, Journal of Clinical
Therapeutics & Medicines, 20: 867-881, 2004).
[0103] The scope of the astaxanthin in the present invention
includes free forms of astaxanthin and/or derivatives such as
esters thereof. Esters of astaxanthin include monoester forms
and/or diester forms. For example, astaxanthin obtained from
Haematococcus pluvialis is known to be in the 3S,3'S-form, and
molecules thereof are known to include many monoester forms with
one fatty acid molecule bonding thereto (Renstrom, B. et al., Fatty
acids of some esterified carotenols, Comp. Biochem. Physiol. B,
Comp. Biochem., 1981, 69, p. 625-627). On the other hand, molecules
of astaxanthin obtained from krill are known to include many
diester forms with two fatty acid molecules bonding thereto
(Yamaguchi, K. et al., The composition of carotenoid pigments in
the Antarctic krill Euphausia superba, Bull. Jap. Sos. Sci. Fish.,
1983, 49, p. 1411-1415).
[0104] Astaxanthin obtained from Phaffia rhodozyma is known to be
in the 3R,3'R-form (Andrewes, A. G. et al., (3R,3'R)-Astaxanthin
from the yeast Phaffia rhodozyma, Phytochem., 1976, 15, p.
1009-1011), which has a structure reverse of that of the
3S,3'S-form, which is commonly found in the nature. The 3R,3'R-form
is present as a non-ester form without forming an ester with a
fatty acid, that is, in a free form (Andrewes, A. G. et al.,
Carotenids of Phaffia rhodozyma, a red pigmented fermenting yeast,
Phytochem., 1976, 15, p. 1003-1007).
[0105] For the astaxanthin applicable in the present invention, any
astaxanthin may be selected without limitation, unless the
characteristics of the present invention are deteriorated, and
examples of such astaxanthin can include natural astaxanthin and
synthesized astaxanthin. Examples of natural astaxanthin can
include astaxanthin-containing extracts themselves obtained from
algae such as Haematococcus spp.; yeasts such as Phaffia sp.;
crustaceans such as shrimps, krill, and crabs; cephalopods such as
squids and octopuses; other fish and shellfish; plants such as
Adonis spp.; bacteria such as Paracoccus sp.N81106, Brevundimonas
sp.SD212, and Erythrobacter sp.PC6; actinomycetes such as Gordonia
sp.KANMONKAZ-1129; labyrinthulomycetes such as Schizochytriuym
sp.KH105; and gene recombinant astaxanthin-producing organisms; and
astaxanthin appropriately purified from any of the
astaxanthin-containing extracts. Preferred is astaxanthin derived
from a microalgae extract extracted from microalgae such as
Haematococcus spp., and more preferred is astaxanthin derived from
a Haematococcus algae extract extracted from Haematococcus algae.
Examples of synthesized astaxanthin can include AstaSana (produced
by Koninklijke DSM N.V.) and Lucantin Pink (registered trademark;
produced by BASF SE). Examples of synthesized astaxanthin obtained
by chemically converting another naturally-occurring carotenoid can
include AstaMarine (produced by PIVEG, Inc.).
[0106] Examples of Haematococcus algae that give natural
astaxanthin can include Haematococcus pluvialis, Haematococcus
lacustris, Haematococcus capensis, Haematococcus deroebakensis, and
Haematococcus zimbabwiensis.
[0107] Preferred methods of culturing these Haematococcus green
algae are closed culture methods, which are free from contamination
with and reproduction of foreign microorganisms and allow less
inclusion of other contaminants, and examples of such culture
methods can include a method of culturing by using an incubator
including a partially open, domed, conical, or cylindrical culture
device and a gas jet unit freely movable in the device
(International Publication No. WO 1999/050384), a method in which
drought stress is applied to Haematococcus algae to induce
encystment of the algae, and astaxanthin is collected from the
culture of the encysted algae (Japanese Patent Laid-Open No.
8-103288), a method of culturing in a closed incubator with
irradiation with light from a light source set in the inside of the
incubator, and a method using a tabular culture tank or a tubular
culture tank.
[0108] The astaxanthin applicable in the present invention may be
an astaxanthin-containing extract obtained by crushing the cell
walls of the above-described Haematococcus algae, for example, in
accordance with a method disclosed in Japanese Patent Laid-Open No.
5-068585, as necessary, and extracting with addition of an organic
solvent such as acetone, ether, chloroform, and alcohol (e.g.,
ethanol, methanol) or an extraction medium/solvent such as
supercritical carbon dioxide; or a product obtained by
appropriately purifying the astaxanthin-containing extract, as
necessary. The astaxanthin content of the astaxanthin-containing
extract is preferably 3 to 40% (w/w), more preferably 3 to 12%
(w/w), and even more preferably 5 to 10% (w/w).
[0109] Examples of the astaxanthin applicable in the present
invention can include commercially available products thereof.
Examples of such commercially available products can include
AstaReal, astavita, and astamate series such as AstaReal Oil 200SS,
AstaReal L10, AstaReal Oil 50F, AstaReal Oil 50FC, AstaReal Oil 5F,
AstaReal P2AF, AstaTROL-X, AstaReal Oil 50FC, AstaReal Powder 20F,
Water-Soluble AstaReal Solution, AstaReal WS Solution, AstaReal
10WS Solution, AstaReal ACT, astavita e, astavita SPORTS, and
astamate (all are registered trademarks; produced by AstaReal Co.,
Ltd., produced by Fuji Chemical Industries Co., Ltd.); ASTOTS
series such as ASTOTS-S, ASTOTS-100, ASTOTS-ECS, ASTPTS-2.0PW, and
ASTOTS-3.0 MB (all ASTOTS are registered trademarks; produced by
FUJIFILM Corporation); BioAstin (registered trademark; produced by
Cyanotech Corporation); Astazine.TM. (produced by BGG Japan);
Astaxanthin Powder 1.5%, Astaxanthin Powder 2.5%, Astaxanthin Oil
5%, and Astaxanthin Oil 10% (Bio Actives Japan Corporation);
ASTAXANTHIN (produced by Oryza Oil & Fat Chemical Co., Ltd.);
SunActive AX (registered trademark; produced by Taiyo Kagaku Co.,
Ltd.); Haematococcus WS30 (produced by YAEGAKI Bio-industry, Inc.);
and AstaMarine (produced by PIVEG, Inc.).
[0110] Each of AstaReal Oil 200SS, AstaReal Oil 50FC, AstaReal
P2AF, AstaTROL-X, AstaReal Oil 50FC, and AstaReal Powder 20F
produced by AstaReal Co., Ltd. and produced by Fuji Chemical
Industries Co., Ltd. has acquired the "Halal certification", and
each of AstaReal Oil 50FC, AstaReal P2AF, AstaTROL-X, AstaReal Oil
50FC, and AstaReal Powder 20F produced by AstaReal Co., Ltd. and
produced by Fuji Chemical Industries Co., Ltd. has acquired the
"Kosher certification". Moreover, AstaReal L10 has acquired Non-GMO
(certification of non-genetically modified organisms).
[0111] Additionally, the emulsion composition according to the
present invention contains an emulsifier (polyglycerin fatty acid
ester and/or sucrose fatty acid ester) being any combination of the
following (a), (b), (c), (d), (e), (f), (g), (h), (i), and (j):
(a) tetraglycerin monooleate and decaglycerin monolaurate
(decaglyceryl monolaurate); (b) tetraglycerin monooleate and
sucrose stearate; (c) tetraglycerin monooleate and sucrose laurate;
(d) decaglycerin monolaurate and sucrose laurate; (e) sucrose
stearate and sucrose laurate; (f) tetraglycerin monooleate,
decaglycerin monolaurate, and sucrose stearate; (g) tetraglycerin
monooleate, decaglycerin monolaurate, and sucrose laurate; (h)
tetraglycerin monooleate, sucrose stearate, and sucrose laurate;
(i) decaglycerin monolaurate, sucrose stearate, and sucrose
laurate; and (j) tetraglycerin monooleate, decaglycerin
monolaurate, sucrose stearate, and sucrose laurate.
[0112] Examples of the tetraglycerin monooleate, decaglycerin
monolaurate, sucrose stearate, and sucrose laurate applicable in
the present invention can include commercially available products
thereof. Examples of such commercially available products can
include SY-Glyster FMO-3S (produced by Sakamoto Yakuhin Kogyo Co.,
Ltd.) for tetraglycerin monooleate; NIKKOL DECAGLYN 1-L (produced
by Nikko Chemicals Co., Ltd.), RYOTO Polygly Ester L-10D (produced
by Mitsubishi-Kagaku Foods Corp.), and SY-Glyster ML-750 (produced
by Sakamoto Yakuhin Kogyo Co., Ltd.) for decaglycerin monolaurate;
RYOTO Sugar Ester (S-070, S-170, S-270, S-370, S-370F, S-570,
S-770, S-970, S-1170, S-1170F, S-1570, S-1670; produced by
Mitsubishi-Kagaku Foods Corp.) and DK ESTER SS (produced by DKS Co.
Ltd.) for sucrose stearate; and RYOTO Sugar Ester (L-195, L-595,
L-1695, LWA-1570; produced by Mitsubishi-Kagaku Foods Corp.) and DK
ESTER S-L18A (produced by DKS Co. Ltd.) for sucrose laurate.
[0113] The emulsion composition according to the present invention
may contain an additional polyglycerin fatty acid ester differing
from tetraglycerin monooleate and/or decaglycerin monolaurate. Any
such polyglycerin fatty acid ester may be selected without
limitation, unless the characteristics of the present invention are
deteriorated, and examples thereof can include an ester of a
polyglycerin with an average degree of polymerization of 2 or
higher and citric acid, caprylic acid, capric acid, lauric acid,
myristic acid, palmitic acid, stearic acid, oleic acid, linoleic
acid, pentastearic acid, monoisostearic acid, diisostearic acid,
pentaisostearic acid, or pentaoleic acid, more specifically,
hexaglycerin monooleate, hexaglycerin monostearate, hexaglycerin
monopalmitate, hexaglycerin monomyristate, hexaglycerin
monolaurate, decaglycerin monooleate, decaglycerin monostearate,
decaglycerin monopalmitate, decaglycerin monomyristate,
decaglycerin monolaurate, glycerin stearate citrate, decaglycerin
distearate, tetraglycerin monostearate, tetraglycerin tristearate,
hexaglycerin monooleate, hexaglycerin monolaurate, hexaglycerin
monomyristate, hexaglycerin monostearate, hexaglycerin tristearate,
hexaglycerin monopalmitate, decaglycerin monomyristate,
decaglycerin monostearate, decaglycerin monolaurate, decaglycerin
monopalmitate, decaglycerin distearate, decaglycerin trioleate,
decaglycerin tristearate, decaglycerin pentastearate, decaglycerin
monoisostearate, decaglycerin diisostearate, decaglycerin
pentaisostearate, and decaglycerin pentaoleate. One or more
polyglycerin fatty acid esters selected from the group consisting
of those polyglycerin fatty acid esters may be contained.
[0114] The emulsion composition according to the present invention
may contain an additional sucrose fatty acid ester differing from
sucrose stearate and/or sucrose laurate. Any such sucrose fatty
acid ester may be selected without limitation, unless the
characteristics of the present invention are deteriorated.
Preferred are sucrose fatty acid esters having high hydrophilicity
and superior water dispersibility, and examples thereof can include
a sucrose fatty acid ester in which a fatty acid having 6 to 22
carbon atoms is bonding to one or more of the hydroxy groups in
sucrose through an ester bond, more specifically, sucrose
myristate, sucrose palmitate, sucrose oleate, and sucrose erucate.
One or more sucrose fatty acid esters selected from the group
consisting of those sucrose fatty acid esters may be contained.
[0115] Further, the emulsion composition according to the present
invention may contain an emulsifier other than the above-described
polyglycerin fatty acid ester and/or sucrose fatty acid ester. Any
such emulsifier may be selected without limitation, unless the
characteristics of the present invention are deteriorated, and
examples thereof can include various emulsifiers conventionally
used for foods and beverages, and so on, specifically, fatty acid
monoglyceride, fatty acid diglyceride, fatty acid triglyceride,
propylene glycol fatty acid ester, lecithin, chemically modified
starches, sorbitan fatty acid ester, succinate fatty acid ester,
Quillaja extract, gum arabic, gum tragacanth, guar gum, karaya gum,
xanthan gum, pectin, alginic acid and salts thereof, carrageenan,
gelatin, casein, saponin, and sterols. One or more emulsifiers
selected from the group consisting of those emulsifiers may be
contained.
[0116] If containing decaglycerin monolaurate and sucrose stearate,
however, the emulsion composition according to the present
invention is free of lecithin.
[0117] Additionally, the emulsion composition according to the
present invention may contain an alcohol. Any alcohol may be
selected without limitation, unless the characteristics of the
present invention are deteriorated, and examples thereof can
include lower alcohols, higher alcohols, and polyhydric alcohols,
more specifically, monohydric alcohols such as ethanol, propanol,
isopropanol, isobutyl alcohol, and t-butyl alcohol; dihydric
alcohols such as ethylene glycol, propylene glycol, trimethylene
glycol, 1,2-butylene glycol, 1,3-butylene glycol, tetramethylene
glycol, 2,3-butylene glycol, pentamethylene glycol,
2-butene-1,4-diol, hexylene glycol, and octylene glycol; trihydric
alcohols such as glycerin and trimethylolpropane; tetrahydric
alcohols such as pentaerythritol such as 1,2,6-hexanetriol;
pentahydric alcohols such as xylitol; hexahydric alcohols such as
sorbitol and mannitol; polyhydric alcohol polymers such as
diethylene glycol, dipropylene glycol, triethylene glycol,
polypropylene glycol, tetraethylene glycol, diglycerin,
polyethylene glycol, triglycerin, tetraglycerin, and polyglycerin;
higher alcohols such as batyl alcohol, cetanol, palmitoleyl
alcohol, heptadecanol, 1-heptadecanol, stearyl alcohol, isostearyl
alcohol, elaidyl alcohol, oleyl alcohol, linoleyl alcohol,
elaidolinoleyl alcohol, linolenyl alcohol, elaidolinolenyl alcohol,
ricinoleyl alcohol, nonadecyl alcohol, arachidyl alcohol,
heneicosanol, behenyl alcohol, and erucyl alcohol; dihydric alcohol
alkyl ethers such as ethylene glycol monomethyl ether, ethylene
glycol monoethyl ether, ethylene glycol monobutyl ether, ethylene
glycol monophenyl ether, ethylene glycol monohexyl ether, ethylene
glycol mono(2-methylhexyl) ether, ethylene glycol isoamyl ether,
ethylene glycol benzyl ether, ethylene glycol isopropyl ether,
ethylene glycol dimethyl ether, ethylene glycol diethyl ether,
ethylene glycol dibutyl ether, diethylene glycol monomethyl ether,
diethylene glycol monoethyl ether, diethylene glycol monobutyl
ether, diethylene glycol dimethyl ether, diethylene glycol diethyl
ether, diethylene glycol butyl ether, diethylene glycol methyl
ethyl ether, triethylene glycol monomethyl ether, triethylene
glycol monoethyl ether, propylene glycol monomethyl ether,
propylene glycol monoethyl ether, propylene glycol monobutyl ether,
propylene glycol isopropyl ether, dipropylene glycol methyl ether,
dipropylene glycol ethyl ether, and dipropylene glycol butyl ether;
dihydric alcohol ether esters such as ethylene glycol monomethyl
ether acetate, ethylene glycol monoethyl ether acetate, ethylene
glycol monobutyl ether acetate, ethylene glycol monophenyl ether
acetate, ethylene glycol diadipate, ethylene glycol disuccinate,
diethylene glycol monoethyl ether acetate, diethylene glycol
monobutyl ether acetate, propylene glycol monomethyl ether acetate,
propylene glycol monoethyl ether acetate, propylene glycol
monopropyl ether acetate, and propylene glycol monophenyl ether
acetate; glycerin monoalkyl ethers; sugar alcohols such as
sorbitol, maltitol, maltotriose, mannitol, sucrose, erythritol,
glucose, fructose, starch sugar, maltose, xylitose, and reduced
alcohol from starch sugar; Glysolid; and other alcohols including
tetrahydrofurfuryl alcohol such as POE-tetrahydrofurfuryl alcohol,
POP-butyl ether, POP/POE-butyl ether, tripolyoxypropylene glycerin
ether, POP-glycerin ether, POP-glycerin ether phosphate, and
POP/POE-pentane erythritol ether. One or more alcohols selected
from the group consisting of those alcohols may be contained.
Preferred are alcohols that enhance homogeneity of emulsifiers, and
specifically, more preferred are monohydric alcohols such as
methanol and ethanol, dihydric alcohols such as propylene glycol,
and sugar alcohols such as xylitol, sorbitol, lactitol, and
erythritol.
[0118] Additionally, the emulsion composition according to the
present invention may contain a mineral. Any mineral may be
selected without limitation, unless the characteristics of the
present invention are deteriorated, and examples of thereof can
include organic acid salts and inorganic acid salts, minerals
blended as food additives typified by chemically synthesized
products, and minerals blended from food materials such as extracts
derived from various foods and yeasts, more specifically, calcium,
phosphorus, copper, zinc, manganese, chromium, molybdenum,
selenium, iron, sodium, potassium, magnesium, iodine, sodium
phosphate, sodium hydrogen phosphate, sodium citrate, and potassium
phosphate. One or more minerals selected from the group consisting
of those minerals may be contained. Preferred are, however, zinc
yeast and minerals derived from yeasts such as zinc yeast.
[0119] Additionally, the emulsion composition according to the
present invention may contain a vitamin. Any vitamin may be
selected without limitation, unless the characteristics of the
present invention are deteriorated, and examples of thereof can
include fat-soluble vitamins and water-soluble vitamins,
specifically, vitamins A such as retinol, retinal, and retinoic
acid, and derivatives thereof; vitamins D such as ergocalciferol
and cholecalciferol; vitamins E such as tocopherol and tocotrienol;
vitamins K such as phylloquinone and menaquinone; vitamins B1 such
as thiamine hydrochloride; vitamins B2 such as riboflavin and
flavin-adenine dinucleotide; niacins such as nicotinic acid and
nicotinamide; pantothenic acid compounds such as pantothenic acid,
calcium pantothenate, and pantothenyl alcohol (panthenol); vitamins
B6 such as pyridoxine, pyridoxal, and pyridoxamine; biotin
compounds such as biotin and biocytin; folic acid compounds such as
folic acid; vitamins B12 such as cyanocobalamin; vitamins C
(ascorbic acid and derivatives thereof) such as sodium ascorbyl
phosphate, magnesium ascorbyl phosphate, ascorbyl glucoside, and
ascorbyl tetra(2-hexyldecanoate); and other vitamin-like factors
such as carnitine, ferulic acid, orotic acid, and .gamma.-oryzanol.
One or more vitamins selected from the group consisting of those
vitamins may be contained. Preferred are, however, vitamins C and
vitamins E.
[0120] Additionally, the emulsion composition according to the
present invention may contain an oil or fat as a fat-soluble
component. Any oil or fat may be selected without limitation,
unless the characteristics of the present invention are
deteriorated, and examples thereof can include oils, which are
liquid at room temperature, and fats, which are solid at room
temperature, and mixtures of them. Examples of liquid oils include
olive oil, Camellia oil, macadamia nut oil, castor oil, avocado
oil, evening primrose oil, turtle oil, corn oil, mink oil, rapeseed
oil, egg-yolk oil, sesame oil, persic oil, wheat germ oil, Camellia
sinensis leaf oil, linseed oil, safflower oil, cottonseed oil,
perilla oil, soybean oil, peanut oil, Camellia sinensis seed oil,
torreya seed oil, rice bran oil, Chinese paulownia oil, Japanese
paulownia oil, jojoba oil, germ oil, glycerin trioctanoate,
glycerin triisopalmitate, salad oil, safflower oil (Carthamus
tinctorius oil), palm oil, coconut oil, peanut oil, almond oil,
hazelnut oil, walnut oil, and grape seed oil. Examples of solid
fats include beef tallow, hydrogenated beef tallow, neatsfoot oil,
beef bone fat, mink oil, egg-yolk oil, lard, horse fat, mutton
tallow, hydrogenated oil, cocoa butter, coconut oil, hydrogenated
coconut oil, palm oil, hydrogenated palm oil, Japan wax, Japan wax
kernel oil, and hydrogenated castor oil. One or more oils or fats
selected from the group consisting of those oils and fats may be
contained.
[0121] Further, medium chain fatty acid triglyceride is preferably
used as the oil or fat. Medium chain fatty acid glyceride refers to
a lipid formed by bonding a saturated fatty acid having 6 to 12
carbon atoms, specifically, any of caproic acid, caprylic acid,
capric acid, and lauric acid to glycerol via an ester bond. The
number of fatty acid molecules bonding to glycerol via an ester
bond may be any of 1 to 3, and a mixture of medium chain fatty acid
glycerides with different numbers of fatty acid molecules is
acceptable. That is, monoglyceride, diglyceride, and triglyceride
are all acceptable, and any mixture of them is also acceptable.
Medium chain fatty acid glycerides with a high unsaturated fatty
acid content (e.g., olive oil, safflower oil) are liquid at room
temperature, and those with a high saturated fatty acid content
(e.g., coconut oil, palm oil) are solid at room temperature. Medium
chain fatty acid glycerides are contained in palm oil, coconut oil,
and so on, and hence these are also preferably used. If a
Haematococcus algae extract containing 18% by weight or more of
astaxanthin is used, stable micelles can be formed by blending the
above-described oil or fat.
[0122] Additionally, the emulsion composition according to the
present invention may contain a radical scavenger. A radical
scavenger is an excipient to play a role of preventing the
generation of radicals and capturing generated radicals as quickly
as possible to stop chain reaction (source: "The handbook of oil
chemistry: lipids and surfactants, 4th Edition", Japan Oil
Chemists' Society (Ed.), 2001). Known as a direct method for
confirming functions as a radical scavenger is a method of mixing
with a reagent and measuring capture of radicals by using a
spectrometer or an ESR (electron spin resonance spectrometer).
[0123] Any compound applicable as a radical scavenger may be
selected without limitation, unless the characteristics of the
present invention are deteriorated, and compounds that function as
a radical scavenger among antioxidants described in "Ko-Sanka-Zai
no Riron to Jissai (Translated title: "Theory and Practical Use of
Antioxidants", Kazimoto, Sanshu Shobo, 1984) and "Sanka-Boshi-Zai
Handbook" (Translated title: "Handbook of Antioxidants", Saruwatari
et al., TAISEISHA LTD., 1976) may be used. Specific examples
thereof can include compounds having a phenolic hydroxy group;
amine compounds including phenylenediamine such as
diphenyl-p-phenylenediamine and 4-amino-p-diphenylamine; ascorbic
acid; and oil-soluble derivatives of erythorbic acid, and specific
examples of compounds having a phenolic hydroxy group can include
gum guaiac; nordihydroguaiaretic acid (NDGA); gallates such as
propyl gallate, butyl gallate, and octyl gallate; BHT
(butylhydroxytoluene); BHA (butylhydroxyanisole); tocopherols such
as mix tocopherol; and bisphenols. One or more compounds selected
from the group consisting of those compounds applicable as a
radical scavenger may be contained. However, tocopherols are
preferred.
[0124] Additionally, the emulsion composition according to the
present invention may contain a polyol. Any polyol may be selected
without limitation, unless the characteristics of the present
invention are deteriorated, and examples thereof include polyols
that have viscosity-adjustment function and lower interfacial
tension between water and oil or fat components, allowing the
interface to easily spread to facilitate formation of a stable
emulsion composition, more specifically, dihydric or higher-hydric
alcohols such as glycerin, diglycerin, triglycerin, polyglycerin,
3-methyl-1,3-butanediol, 1,3-butylene glycol, isoprene glycol,
polyethylene glycol, 1,2-pentanediol, 1,2-hexanediol, propylene
glycol, dipropylene glycol, polypropylene glycol, ethylene glycol,
diethylene glycol, pentaerythritol, neopentyl glycol, maltitol,
reduced sugar syrup, fructose, glucose, sucrose, lactitol,
Palatinit, erythritol, sorbitol, mannitol, xylitol, xylose,
glucose, lactose, mannose, maltose, galactose, fructose, inositol,
pentaerythritol, maltotriose, sorbitol, sorbitan, trehalose, starch
sugar, and reduced alcohol from starch sugar. One of these polyols
may be used singly, and one or more of them may be used in
combination. However, it is preferred to contain one or more
selected from glycerin, diglycerin, propylene glycol, ethylene
glycol, 1,3-butylene glycol, polyethylene glycol, sorbitol,
mannitol, dipropylene glycol, and sorbitan, and it is more
preferred to contain at least glycerin.
[0125] Additionally, the emulsion composition of the present
invention contains water in some cases. This water is not limited
to particular water, and any water used for foods, drugs, and
cosmetics, such as purified water, pure water, ion-exchanged water,
alkaline ionized water, deep seawater, vibrated water, and natural
water, may be used.
[0126] Further, the emulsion composition according to the present
invention may contain, unless the characteristics of the present
invention are deteriorated, any substance, for example, any of
glycerophospholipids such as phosphatidic acid, bisphosphatidic
acid, lecithin (phosphatidylcholine), phosphatidylethanolamine,
phosphatidylmethylethanolamine, phosphatidylserine,
phosphatidylinositol, phosphatidylglycerin, and
diphosphatidylglycerin (cardiolipin), and hydrogenated or
hydroxylated products of them; lyso compounds such as lysolecithin,
lysophosphatidic acid, lysophosphatidylglycerin,
lysophosphatidylinositol, lysophosphatidylethanolamine,
lysophosphatidylmethylethanolamine, lysophosphatidylcholine
(lysolecithin), and lysophosphatidylserine; lecithins derived from
plants such as soybean, corn, peanut, rapeseed, and wheat, those
derived from animals such as egg yolk and bovines, and those
derived from microorganisms such as Escherichia coli;
sphingophospholipids such as sphingomyelin (phospholipids, up to
here); ascorbic acid and ascorbic acid derivatives and salts
thereof such as L-ascorbic acid, sodium L-ascorbate, potassium
L-ascorbate, calcium L-ascorbate, L-ascorbyl phosphate, magnesium
L-ascorbyl phosphate, L-ascorbyl sulfate, disodium L-ascorbyl
sulfate, and L-ascorbyl 2-glucoside; erythorbic acid and erythorbic
acid derivatives and salts thereof such as erythorbic acid, sodium
erythorbate, potassium erythorbate, calcium erythorbate, erythorbyl
phosphate, and erythorbyl sulfate; flavonoids (e.g., catechin,
anthocyanin, flavone, isoflavone, flavane, flavanone, rutin,
glycosides thereof), phenols (e.g., chlorogenic acid, ellagic acid,
gallic acid, propyl gallate), and polyphenols such as lignans,
curcumins, and coumarins (antioxidants, up to here); and other
flavors, sweeteners, acidulants, and coloring agents. One of these
may be used singly, and one or more of them may be used in
combination thereof.
[0127] Additionally, the emulsion composition of the present
invention may have a self-emulsifying property. Self-emulsification
in the present invention, which is also called spontaneous
emulsification, refers to spontaneous formation of an emulsion
through contact with an aqueous medium or digestive juice, without
need of external force. If the emulsion composition of the present
invention has a self-emulsifying property, the emulsion composition
is capable of forming an emulsion stable in solutions containing
more than 40%, 50%, 60%, 70%, 75%, 80%, 85%, or 90% (w/w) of water.
In one preferred mode of the present invention, the water content
is about 0.01 to 7 parts by weight to 100 parts by weight of the
total of the emulsion composition.
[0128] A method for producing the emulsion composition according to
the present invention includes the following steps (i) to (iii):
(i) mixing and dissolving at least sucrose fatty acid ester, and,
as necessary, an additional water-soluble substance such as a
water-soluble emulsifier, a polyol, a water-soluble mineral, and a
water-soluble vitamin in water to obtain an aqueous phase (aqueous
phase preparation step); (ii) mixing and dissolving at least a
carotenoid and a sucrose fatty acid ester and/or polyglycerin fatty
acid ester, and, as necessary, an additional fat-soluble substance
such as a fat-soluble emulsifier, an oil or fat, a compound
applicable as a radical scavenger, a fat-soluble mineral, and a
fat-soluble vitamin to obtain an oil phase (oil phase preparation
step); and (iii) subsequently mixing the aqueous phase and the oil
phase together to obtain a mixed solution and subjecting the
resulting mixed solution to emulsification and dispersion to obtain
an emulsion composition (emulsion composition preparation
step).
[0129] When no sucrose fatty acid ester is used (mixed/dissolved)
in aqueous phase preparation step (i), aqueous phase preparation
step (i) is a step of mixing and dissolving water, and, as
necessary, an additional water-soluble substance such as a
water-soluble emulsifier, a polyol, a water-soluble mineral, and a
water-soluble vitamin to obtain an aqueous phase, and emulsion
composition preparation step (iii) is a step of mixing water or the
aqueous phase and the oil phase together to obtain an emulsion
composition.
[0130] When no polyglycerin fatty acid ester is used
(mixed/dissolved) in oil phase preparation step (ii), oil phase
preparation step (ii) is a step of mixing and dissolving at least a
carotenoid and an oil or fat, and, as necessary, a sucrose fatty
acid ester and an additional fat-soluble substance such as a
fat-soluble emulsifier, a compound applicable as a radical
scavenger, a fat-soluble mineral, and a fat-soluble vitamin to
obtain an oil phase.
[0131] When at least sucrose stearate is mixed and dissolved in
water in aqueous phase preparation step (i) and at least a
carotenoid and decaglycerin monolaurate are mixed and dissolved in
oil phase preparation step (ii), or when water, and, as necessary,
an additional water-soluble substance such as a water-soluble
emulsifier, a polyol, a water-soluble mineral, and a water-soluble
vitamin are mixed, and at least a carotenoid, sucrose stearate, and
decaglycerin monolaurate are mixed in oil phase preparation step
(ii), lecithin is not mixed and dissolved in oil phase preparation
step (ii).
[0132] Herein, an HLB (Hydrophile-Lipophile Balance) value may be
used as an index to determine whether to use (mix and dissolve) a
sucrose fatty acid ester in the aqueous phase preparation step or
in the oil phase preparation step.
[0133] In this case, a commercially available product is used when
a component to be used is available as a commercially available
product, and if the HLB value of the commercially available product
is clearly shown in a document such as a catalog of commercially
available products, the HLB value shown in the document such as a
catalog is employed.
[0134] If a component to be used is not available as a commercially
available product, or if a component to be used is available as a
commercially available product but the HLB value is not clearly
shown in a document such as a catalog, on the other hand, a value
determined by using Griffin's calculation formula is employed as an
HLB value herein. Griffin's calculation formula uses the value S
(saponification value of ester) and the value N (neutralization
number of fatty acid constituting ester) for calculation of HLB
values. The formula is as follows.
HLB Value=20(1-S/N)
[0135] An HLB value indicates higher hydrophilicity as the HLB
value approaches 20, and higher lipophilicity as the HLB value
approaches 0. Commonly, emulsifiers having an HLB value of lower
than 7 are defined as being lipophilic, and those having an HLB
value of 7 or higher are defined as being hydrophilic.
[0136] Emulsification and dispersion in emulsion composition
preparation step (iii) may be performed by using a common
emulsifier such as a stirrer, Impeller stirring, a homomixer, and a
continuous flow shearing machine.
[0137] Additionally, a soft capsule formulation may be selected as
a dosage form of the emulsion composition according to the present
invention, and the soft capsule formulation is obtained by
enclosing a content containing the emulsion composition according
to the present invention in a soft capsule shell.
[0138] In the present invention, any soft capsule formulation may
be selected without limitation, unless the characteristics of the
present invention are deteriorated, and examples of such soft
capsule formulations can include a capsule molded into a single
container carrying a liquid payload or semisolid containing a drug,
one or two or more excipients, and an optional diluent (e.g.,
including an emulsion formulation formed through
self-emulsification and non-emulsion formulation).
[0139] A method for producing the soft capsule formulation
according to the present invention includes obtaining the emulsion
composition according to (1) or (2) in the above-described manner,
and further includes the step of (iv) subsequently enclosing a
content containing the thus-obtained emulsion composition in a soft
capsule shell (soft capsule enclosure step).
[0140] An exemplary mode of soft capsule enclosure step (iv) in the
present invention includes the following steps (1) to (3): (1)
preparing a capsule content and a base material to form a soft
capsule shell (material preparation step); (2) enclosing the
content in the resulting base material to form a soft capsule
shell, molding the base material, and drying the resultant to
obtain an intermediate formulation (molding step); and (3) drying
the resulting intermediate formulation (drying step).
[0141] "Material preparation step" (1) is a step of preparing a
content containing the emulsion composition according to the
present invention and a base material to form a soft capsule shell,
and the step is as described above.
[0142] "Molding step" (2) is a step of enclosing the content
containing the emulsion composition according to the present
invention in a shell formed with the base material to form a soft
capsule shell, molding the base material, and drying the resultant
to obtain an intermediate formulation. A known method for producing
a soft capsule formulation may be appropriately selected for
enclosure of the content in the base material to form a soft
capsule shell. Examples of such methods can include a plate method
and a rotary die method.
[0143] "Drying step" (3) is a step of drying the intermediate
formulation obtained in the molding step, and a soft capsule
formulation is obtained through this step. A known drying means may
be appropriately selected as a drying means used in the drying
step. Examples of such means can include means with a known dryer
such as a tumbler dryer (rotary drum dryer). Conditions including
temperature and time in the drying step are not limited to
particular conditions, and those according to the content of the
capsule and the type of the base material to form a soft capsule
shell may be appropriately selected.
[0144] In the present invention, any base material to form a soft
capsule shell may be appropriately selected, unless the
characteristics of the present invention are deteriorated, and
examples thereof can include base materials containing as a main
component any of the followings: gelatins such as gelatin, acidic
gelatin, alkaline gelatin, peptide gelatin, low-molecular-weight
gelatin, and gelatin derivatives; agar; and gellan gum. In the case
that gelatin is used as a base material of a soft capsule shell,
the base material is prepared from a gelatin shell solution
containing gelatin, a plasticizer, and water. The soft capsule
shell may contain a plasticizer, unless the characteristics of the
present invention are deteriorated, and examples of such
plasticizers can include glycerin; saccharides such as corn syrup,
sucrose, fructose, sorbitol, and mannitol; glycols such as
propylene glycol and polyethylene glycol; and water-insoluble
celluloses such as microcrystalline cellulose, starches,
low-substituted hydroxypropylcellulose, and ethylcellulose. One of
these plasticizers may be used singly, and one or more of them may
be used in combination thereof.
[0145] In the present invention, the content in the soft capsule
formulation may contain 0.0001% by mass to 98% by mass of the
emulsion composition according to the present invention to the
total amount of the soft capsule formulation. The shape of the soft
capsule formulation is not limited to a particular shape, and
examples thereof can include an oval, an oblong, and a round. To
form any of these shapes, a technique, an apparatus, and so on
well-known in the art may be appropriately applied.
[0146] In the present invention, an excipient component commonly
used in the field of foods and beverages and drugs may be
appropriately blended in the soft capsule formulation (the content
and/or the shell), unless the characteristics of the present
invention are deteriorated. For example, an excipient component may
be appropriately selected for blending from coloring agents such as
dyes and pigments, flavors, sweeteners, taste-masking agents,
odor-masking agents, preservatives, fruit juices, vitamins, animal
and plant extracts, amino acids, minerals, thickeners, pH-adjusting
agents, antiseptics, disintegrants, surfactants, and organic
acids.
Examples
[0147] Hereinafter, the emulsion composition according to the
present invention and the production method therefor will be
described on the basis of Examples. It should be noted that the
technical scope of the present invention is not limited to
embodiments shown in Examples.
1. Preparation of Emulsion Composition
[0148] First, emulsion compositions according to Examples 1 to 42
were prepared as described below. In preparation of emulsion
compositions according to Examples 1 to 42, "AstaReal Oil 200SS
(produced by AstaReal Co., Ltd.)" was used as "20% Haematococcus
algae pigment oil", "AstaReal L10 (produced by AstaReal Co., Ltd.)"
was used as "10% Haematococcus algae pigment oil", and "Lutemax
2020 (produced by OmniActive Health Technologies)" was used as
"lutein/zeaxanthin". "SY-Glyster FMO-3S (produced by Sakamoto
Yakuhin Kogyo Co., Ltd.)" was used as "tetraglycerin monooleate",
"NIKKOL DECAGLYN 1-L (produced by Nikko Chemicals Co., Ltd.)" was
used as "decaglycerin monolaurate (decaglyceryl monolaurate)", "DK
ESTER SS (produced by DKS Co. Ltd.)" and "RYOTO Sugar Ester S-570
(produced by Mitsubishi-Kagaku Foods Corp.)" were used as "sucrose
stearate", and "RYOTO Sugar Ester L-1695 (produced by
Mitsubishi-Kagaku Foods Corp.)" and "RYOTO Sugar Ester L-195
(produced by Mitsubishi-Kagaku Foods Corp.)" were used as "sucrose
laurate". MCT oil was used as medium chain fatty acid
triglyceride.
[1-1] Preparation of Emulsion Composition According to Example
1
[0149] An oil phase was prepared by adding 43 g of 10%
Haematococcus algae pigment oil, 12 g of triglyceride, 2 g of mix
tocopherol, and 18 g of tetraglycerin monooleate, and mixing and
dissolving the resultant. Subsequently, 9.8 g of sucrose laurate
having an HLB value of 16, 1 g of ethanol, and 9 g of glycerin were
added to 5.2 g of purified water and dissolved to prepare an
aqueous phase, and the oil phase and the aqueous phase were then
mixed together to obtain an emulsion composition, which was used as
an emulsion composition according to Example 1.
[1-2] Preparation of Emulsion Composition According to Example
2
[0150] An oil phase was prepared by adding 32 g of 10%
Haematococcus algae pigment oil, 20 g of lutein/zeaxanthin oil, 0.8
g of triglyceride, 2 g of mix tocopherol, and 18 g of tetraglycerin
monooleate, and mixing and dissolving the resultant. Subsequently,
13 g of sucrose laurate having an HLB value of 16, 6 g of propylene
glycol, and 3 g of glycerin were added to 5.2 g of purified water
and dissolved to prepare an aqueous phase, and the oil phase and
the aqueous phase were then mixed together to obtain an emulsion
composition, which was used as an emulsion composition according to
Example 2.
[1-3] Preparation of Emulsion Composition According to Example
3
[0151] An oil phase was prepared by adding 32 g of 10%
Haematococcus algae pigment oil, 20 g of lutein/zeaxanthin oil, 3.8
g of triglyceride, 2 g of mix tocopherol, and 18 g of tetraglycerin
monooleate, and mixing and dissolving the resultant. Subsequently,
10 g of sucrose laurate having an HLB value of 16, 6 g of propylene
glycol, and 3 g of glycerin were added to 5.2 g of purified water
and dissolved to prepare an aqueous phase, and the oil phase and
the aqueous phase were then mixed together to obtain an emulsion
composition, which was used as an emulsion composition according to
Example 3.
[1-4] Preparation of Emulsion Composition According to Example
4
[0152] An oil phase was prepared by adding 32 g of 10%
Haematococcus algae pigment oil, 20 g of lutein/zeaxanthin oil, 7.8
g of triglyceride, 2 g of mix tocopherol, and 18 g of tetraglycerin
monooleate, and mixing and dissolving the resultant. Subsequently,
6 g of sucrose laurate having an HLB value of 16, 6 g of propylene
glycol, and 3 g of glycerin were added to 5.2 g of purified water
and dissolved to prepare an aqueous phase, and the oil phase and
the aqueous phase were then mixed together to obtain an emulsion
composition, which was used as an emulsion composition according to
Example 4.
[1-5] Preparation of Emulsion Composition According to Example
5
[0153] An oil phase was prepared by adding 32 g of 10%
Haematococcus algae pigment oil, 20 g of lutein/zeaxanthin oil,
11.8 g of triglyceride, 2 g of mix tocopherol, and 18 g of
tetraglycerin monooleate, and mixing and dissolving the resultant.
Subsequently, 2 g of sucrose laurate having an HLB value of 16, 6 g
of propylene glycol, and 3 g of glycerin were added to 5.2 g of
purified water and dissolved to prepare an aqueous phase, and the
oil phase and the aqueous phase were then mixed together to obtain
an emulsion composition, which was used as an emulsion composition
according to Example 5.
[1-6] Preparation of Emulsion Composition According to Example
6
[0154] An oil phase was prepared by adding 32 g of 10%
Haematococcus algae pigment oil, 20 g of lutein/zeaxanthin oil,
10.8 g of triglyceride, 2 g of mix tocopherol, and 13.5 g of
tetraglycerin monooleate, and mixing and dissolving the resultant.
Subsequently, 7.5 g of sucrose laurate having an HLB value of 16, 6
g of propylene glycol, and 3 g of glycerin were added to 5.2 g of
purified water and dissolved to prepare an aqueous phase, and the
oil phase and the aqueous phase were then mixed together to obtain
an emulsion composition, which was used as an emulsion composition
according to Example 6.
[1-7] Preparation of Emulsion Composition According to Example
7
[0155] An oil phase was prepared by adding 32 g of 10%
Haematococcus algae pigment oil, 20 g of lutein/zeaxanthin oil, 9.8
g of triglyceride, 2 g of mix tocopherol, and 12 g of tetraglycerin
monooleate, and mixing and dissolving the resultant. Subsequently,
10 g of sucrose laurate having an HLB value of 16, 6 g of propylene
glycol, and 3 g of glycerin were added to 5.2 g of purified water
and dissolved to prepare an aqueous phase, and the oil phase and
the aqueous phase were then mixed together to obtain an emulsion
composition, which was used as an emulsion composition according to
Example 7.
[1-8] Preparation of Emulsion Composition According to Example
8
[0156] An oil phase was prepared by adding 32 g of 10%
Haematococcus algae pigment oil, 20 g of lutein/zeaxanthin oil,
17.8 g of triglyceride, 2 g of mix tocopherol, and 9 g of
tetraglycerin monooleate, and mixing and dissolving the resultant.
Subsequently, 5 g of sucrose laurate having an HLB value of 16, 6 g
of propylene glycol, and 3 g of glycerin were added to 5.2 g of
purified water and dissolved to prepare an aqueous phase, and the
oil phase and the aqueous phase were then mixed together to obtain
an emulsion composition, which was used as an emulsion composition
according to Example 8.
[1-9] Preparation of Emulsion Composition According to Example
9
[0157] An oil phase was prepared by adding 32 g of 10%
Haematococcus algae pigment oil, 20 g of lutein/zeaxanthin oil,
15.8 g of triglyceride, 2 g of mix tocopherol, and 6 g of
tetraglycerin monooleate, and mixing and dissolving the resultant.
Subsequently, 10 g of sucrose laurate having an HLB value of 16, 6
g of propylene glycol, and 3 g of glycerin were added to 5.2 g of
purified water and dissolved to prepare an aqueous phase, and the
oil phase and the aqueous phase were then mixed together to obtain
an emulsion composition, which was used as an emulsion composition
according to Example 9.
[1-10] Preparation of Emulsion Composition According to Example
10
[0158] An oil phase was prepared by adding 32 g of 10%
Haematococcus algae pigment oil, 20 g of lutein/zeaxanthin oil, 3.8
g of triglyceride, 2 g of mix tocopherol, 18 g of tetraglycerin
monooleate, and 10 g of sucrose laurate having an HLB value of 1,
and mixing and dissolving the resultant. Subsequently, 6 g of
propylene glycol and 3 g of glycerin were added to 5.2 g of
purified water and dissolved to prepare an aqueous phase, and the
oil phase and the aqueous phase were then mixed together to obtain
an emulsion composition, which was used as an emulsion composition
according to Example 10. Table 1 shows the formulations of the
above emulsion compositions according to Examples 1 to 10.
TABLE-US-00001 TABLE 1 Exam- Exam- Exam- Exam- Exam- Exam- Exam-
Exam- Exam- Exam- ple 1 ple 2 ple 3 ple 4 ple 5 ple 6 ple 7 ple 8
ple 9 ple 10 Raw material Weight Weight Weight Weight Weight Weight
Weight Weight Weight Weight 20% Haematococcus algae pigment oil --
-- -- -- -- -- -- -- -- -- (AstaRcal Oil 200SS (astaxanthins
content: 20.3%, carotenoids content, excluding astaxanthins: 3.2%,
acyl glycerin content: 59.5%)) 10% Haematococcus algae pigment oil
43 32 32 32 32 32 32 32 32 32 (AstaReal L10 (astaxanthins content:
11.3%, carotenoids content, excluding astaxanthins: 7.5%, of acyl
glycerin content: 70.2%)) Lutcin/zeaxanthin -- 20 20 20 20 20 20 20
20 20 (Lutemax 2020 (produced by OmniActive Health Technologies))
Medium chain fatty acid triglyceride 12 0.8 3.8 7.8 11.8 10.8 9.8
17.8 15.8 3.8 Mix tocopherol 2 2 2 2 2 2 2 2 2 2 Lecithin paste
(lecithin content: 60% or more) -- -- -- -- -- -- -- -- -- --
Tetraglycerin monooleate 18 18 18 18 18 13.5 12 9 6 18 (SY-Glyster
FMO-3S (produced by Sakamoto Yakuhin Kogyo Co., Ltd.)) Decaglycerin
monolaurate -- -- -- -- -- -- -- -- -- -- (NIKKOL DECAGLYN 1-L
(produced by Nikko Chemicals Co., Ltd.)) Sucrose stearate (HLB19)
-- -- -- -- -- -- -- -- -- -- (DK ESTER SS (produced by DKS Co.
Ltd.)) Sucrose stearate (HLB5) (RYOTO Sugar Ester S-570 -- -- -- --
-- -- -- -- -- -- (produced by Mitsubishi-Kagaku Foods Corp.))
Sucrose laurate (HLB16) ("RYOTO Sugar Ester L- 9.8 13 10 6 2 7.5 10
5 10 -- 1695 (produced by Mitsubishi-Kagaku Foods Corp.)) Sucrose
laurate (HLB1) "RYOTO Sugar Ester L-195 -- -- -- -- -- -- -- -- --
10 (produced by Mitsubishi-Kagaku Foods Corp.)) Purified water 5.2
5.2 5.2 5.2 5.2 5.2 5.2 5.2 5.2 5.2 Ethanol 1 -- -- -- -- -- -- --
-- -- Propylene glycol -- 6 6 6 6 6 6 6 6 6 Glycerin 9 3 3 3 3 3 3
3 3 3 Total (g) 100 100 100 100 100 100 100 100 100 100
[1-11] Preparation of Emulsion Composition According to Example
11
[0159] An oil phase was prepared by adding 43 g of 10%
Haematococcus algae pigment oil, 12 g of triglyceride, 2 g of mix
tocopherol, and 18 g of tetraglycerin monooleate, and mixing and
dissolving the resultant. Subsequently, 9.8 g of sucrose stearate
having an HLB value of 19, 1 g of ethanol, and 9 g of glycerin were
added to 5.2 g of purified water and dissolved to prepare an
aqueous phase, and the oil phase and the aqueous phase were then
mixed together to obtain an emulsion composition, which was used as
an emulsion composition according to Example 11.
[1-12] Preparation of Emulsion Composition According to Example
12
[0160] An oil phase was prepared by adding 32 g of 10%
Haematococcus algae pigment oil, 20 g of lutein/zeaxanthin oil, 7.8
g of triglyceride, 2 g of mix tocopherol, and 18 g of tetraglycerin
monooleate, and mixing and dissolving the resultant. Subsequently,
6 g of sucrose stearate having an HLB value of 19, 6 g of propylene
glycol, and 3 g of glycerin were added to 5.2 g of purified water
and dissolved to prepare an aqueous phase, and the oil phase and
the aqueous phase were then mixed together to obtain an emulsion
composition, which was used as an emulsion composition according to
Example 12.
[1-13] Preparation of Emulsion Composition According to Example
13
[0161] An oil phase was prepared by adding 32 g of 10%
Haematococcus algae pigment oil, 20 g of lutein/zeaxanthin oil,
11.8 g of triglyceride, 2 g of mix tocopherol, and 18 g of
tetraglycerin monooleate, and mixing and dissolving the resultant.
Subsequently, 2 g of sucrose stearate having an HLB value of 19, 6
g of propylene glycol, and 3 g of glycerin were added to 5.2 g of
purified water and dissolved to prepare an aqueous phase, and the
oil phase and the aqueous phase were then mixed together to obtain
an emulsion composition, which was used as an emulsion composition
according to Example 13.
[1-14] Preparation of Emulsion Composition According to Example
14
[0162] An oil phase was prepared by adding 32 g of 10%
Haematococcus algae pigment oil, 20 g of lutein/zeaxanthin oil, 9.8
g of triglyceride, 2 g of mix tocopherol, and 12 g of tetraglycerin
monooleate, and mixing and dissolving the resultant. Subsequently,
10 g of sucrose stearate having an HLB value of 19, 6 g of
propylene glycol, and 3 g of glycerin were added to 5.2 g of
purified water and dissolved to prepare an aqueous phase, and the
oil phase and the aqueous phase were then mixed together to obtain
an emulsion composition, which was used as an emulsion composition
according to Example 14.
[1-15] Preparation of Emulsion Composition According to Example
15
[0163] An oil phase was prepared by adding 32 g of 10%
Haematococcus algae pigment oil, 20 g of lutein/zeaxanthin oil,
15.8 g of triglyceride, 2 g of mix tocopherol, and 6 g of
tetraglycerin monooleate, and mixing and dissolving the resultant.
Subsequently, 10 g of sucrose stearate having an HLB value of 19, 6
g of propylene glycol, and 3 g of glycerin were added to 5.2 g of
purified water and dissolved to prepare an aqueous phase, and the
oil phase and the aqueous phase were then mixed together to obtain
an emulsion composition, which was used as an emulsion composition
according to Example 15. Table 2 shows the formulations of the
above emulsion compositions according to Examples 11 to 15.
TABLE-US-00002 TABLE 2 Example 11 Example 12 Example 13 Example 14
Example 15 Raw material Weight Weight Weight Weight Weight 20%
Haematococcus algae pigment oil -- -- -- -- -- (AstaReal Oil 200SS
(astaxanthins content: 20.3%, carotenoids content, excluding
astaxanthins: 3.2%, acyl glycerin content: 59.5%)) 10%
Haematococcus algae pigment oil 43 32 32 32 32 (AstaReal L10
(astaxanthins content: 11.3%, carotenoids content, excluding
astaxanthins: 7.5%, of acyl glycerin content: 70.2%))
Lutein/zeaxanthin -- 20 20 20 20 (Lutemax 2020 (produced by
OmniActive Health Technologies)) Medium chain fatty acid
triglyceride 12 7.8 11.8 9.8 15.8 Mix tocopherol 2 2 2 2 2 Lecithin
paste (lecithin content: 60% or more) -- -- -- -- -- Tetraglycerin
monooleate 18 18 18 12 6 (SY-Glyster FMO-3S (produced by Sakamoto
Yakuhin Kogyo Co., Ltd.)) Decaglycerin monolaurate -- -- -- -- --
(NIKKOL DECAGLYN 1-L (produced by Nikko Chemicals Co., Ltd.))
Sucrose stearate (HLB19) 9.8 6 2 10 10 (DK ESTER SS (produced by
DKS Co. Ltd.)) Sucrose stearate (HLB5) (RYOTO Sugar Ester S-570
(produced by -- -- -- -- -- Mitsubishi-Kagaku Foods Corp.)) Sucrose
laurate (HLB16) ("RYOTO Sugar Ester L-1695 (produced by -- -- -- --
-- Mitsubishi-Kagaku Foods Corp.)) Sucrose laurate (HLB1) "RYOTO
Sugar Ester L-195 (produced by -- -- -- -- -- Mitsubishi-Kagaku
Foods Corp.)) Purified water 5.2 5.2 5.2 5.2 5.2 Ethanol 1 -- -- --
-- Propylene glycol -- 6 6 6 6 Glycerin 9 3 3 3 3 Total (g) 100 100
100 100 100
[1-16] Preparation of Emulsion Composition According to Example
16
[0164] An oil phase was prepared by adding 43 g of 10%
Haematococcus algae pigment oil, 12 g of triglyceride, 2 g of mix
tocopherol, 18 g of tetraglycerin monooleate, and 9.8 g of
decaglycerin monolaurate, and mixing and dissolving the resultant.
Subsequently, 1 g of ethanol and 9 g of glycerin were added to 5.2
g of purified water and dissolved to prepare an aqueous phase, and
the oil phase and the aqueous phase were then mixed together to
obtain an emulsion composition, which was used as an emulsion
composition according to Example 16.
[1-17] Preparation of Emulsion Composition According to Example
17
[0165] An oil phase was prepared by adding 32 g of 10%
Haematococcus algae pigment oil, 21 g of lutein/zeaxanthin oil, 1 g
of triglyceride, 3 g of mix tocopherol, 18 g of tetraglycerin
monooleate, and 9.8 g of decaglycerin monolaurate, and mixing and
dissolving the resultant. Subsequently, 1 g of ethanol and 9 g of
glycerin were added to 5.2 g of purified water and dissolved to
prepare an aqueous phase, and the oil phase and the aqueous phase
were then mixed together to obtain an emulsion composition, which
was used as an emulsion composition according to Example 17.
[1-18] Preparation of Emulsion Composition According to Example
18
[0166] An oil phase was prepared by adding 32 g of 10%
Haematococcus algae pigment oil, 21 g of lutein/zeaxanthin oil, 1 g
of triglyceride, 3 g of mix tocopherol, 18 g of tetraglycerin
monooleate, and 9.8 g of decaglycerin monolaurate, and mixing and
dissolving the resultant. Subsequently, 1 g of propylene glycol and
9 g of glycerin were added to 5.2 g of purified water and dissolved
to prepare an aqueous phase, and the oil phase and the aqueous
phase were then mixed together to obtain an emulsion composition,
which was used as an emulsion composition according to Example
18.
[1-19] Preparation of Emulsion Composition According to Example
19
[0167] An oil phase was prepared by adding 24 g of 10%
Haematococcus algae pigment oil, 15.5 g of lutein/zeaxanthin oil,
2.3 g of triglyceride, 2 g of mix tocopherol, 27 g of tetraglycerin
monooleate, and 15 g of decaglycerin monolaurate, and mixing and
dissolving the resultant. Subsequently, 6 g of propylene glycol and
3 g of glycerin were added to 5.2 g of purified water and dissolved
to prepare an aqueous phase, and the oil phase and the aqueous
phase were then mixed together to obtain an emulsion composition,
which was used as an emulsion composition according to Example 19.
Table 3 shows the formulations of the above emulsion compositions
according to Examples 16 to 19.
TABLE-US-00003 TABLE 3 Example 16 Example 17 Example 18 Example 19
Raw material Weight Weight Weight Weight 20% Haematococcus algae
pigment oil -- -- -- -- (AstaReal Oil 200SS (astaxanthins content:
20.3%, carotenoids content, excluding astaxanthins: 3.2%, acyl
glycerin content: 59.5%)) 10% Haematococcus algae pigment oil 43 32
32 24 (AstaReal L10 (astaxanthins content: 11.3%, carotenoids
content, excluding astaxanthins: 7.5%, of acyl glycerin content:
70.2%)) Lutein/zeaxanthin -- 21 21 15.5 (Lutemax 2020 (produced by
OmniActive Health Technologies)) Medium chain fatty acid
triglyceride 12 1 1 2.3 Mix tocopherol 2 3 3 2 Lecithin paste
(lecithin content: 60% or more) -- -- -- -- Tetraglycerin
monooleate 18 18 18 27 (SY-Glyster FMO-3S (produced by Sakamoto
Yakuhin Kogyo Co., Ltd.)) Decaglycerin monolaurate 9.8 9.8 9.8 15
(NIKKOL DECAGLYN 1-L (produced by Nikko Chemicals Co., Ltd.))
Sucrose stearate (HLB19) -- -- -- -- (DK ESTER SS (produced by DKS
Co. Ltd.)) Sucrose stearate (HLB5) (RYOTO Sugar Ester S-570
(produced by -- -- -- -- Mitsubishi-Kagaku Foods Corp.)) Sucrose
laurate (HLB16) ("RYOTO Sugar Ester L-1695 (produced by -- -- -- --
Mitsubishi-Kagaku Foods Corp.)) Sucrose laurate (HLB1) "RYOTO Sugar
Ester L-195 (produced by -- -- -- -- Mitsubishi-Kagaku Foods
Corp.)) Purified water 5.2 5.2 5.2 5.2 Ethanol 1 1 -- -- Propylene
glycol -- -- 1 6 Glycerin 9 9 9 3 Total (g) 100 100 100 100
[1-20] Preparation of Emulsion Composition According to Example
20
[0168] An oil phase was prepared by adding 32 g of 10%
Haematococcus algae pigment oil, 20 g of lutein/zeaxanthin oil, 6.8
g of triglyceride, 2 g of mix tocopherol, and 15 g of decaglycerin
monolaurate, and mixing and dissolving the resultant. Subsequently,
10 g of sucrose laurate having an HLB value of 16, 6 g of propylene
glycol, and 3 g of glycerin were added to 5.2 g of purified water
and dissolved to prepare an aqueous phase, and the oil phase and
the aqueous phase were then mixed together to obtain an emulsion
composition, which was used as an emulsion composition according to
Example 20.
[1-21] Preparation of Emulsion Composition According to Example
21
[0169] An oil phase was prepared by adding 32 g of 10%
Haematococcus algae pigment oil, 20 g of lutein/zeaxanthin oil,
10.8 g of triglyceride, 2 g of mix tocopherol, and 15 g of
decaglycerin monolaurate, and mixing and dissolving the resultant.
Subsequently, 6 g of sucrose laurate having an HLB value of 16, 6 g
of propylene glycol, and 3 g of glycerin were added to 5.2 g of
purified water and dissolved to prepare an aqueous phase, and the
oil phase and the aqueous phase were then mixed together to obtain
an emulsion composition, which was used as an emulsion composition
according to Example 21.
[1-22] Preparation of Emulsion Composition According to Example
22
[0170] An oil phase was prepared by adding 32 g of 10%
Haematococcus algae pigment oil, 20 g of lutein/zeaxanthin oil,
14.8 g of triglyceride, 2 g of mix tocopherol, and 15 g of
decaglycerin monolaurate, and mixing and dissolving the resultant.
Subsequently, 2 g of sucrose laurate having an HLB value of 16, 6 g
of propylene glycol, and 3 g of glycerin were added to 5.2 g of
purified water and dissolved to prepare an aqueous phase, and the
oil phase and the aqueous phase were then mixed together to obtain
an emulsion composition, which was used as an emulsion composition
according to Example 22.
[1-23] Preparation of Emulsion Composition According to Example
23
[0171] An oil phase was prepared by adding 32 g of 10%
Haematococcus algae pigment oil, 20 g of lutein/zeaxanthin oil,
11.8 g of triglyceride, 2 g of mix tocopherol, and 10 g of
decaglycerin monolaurate, and mixing and dissolving the resultant.
Subsequently, 10 g of sucrose laurate having an HLB value of 16, 6
g of propylene glycol, and 3 g of glycerin were added to 5.2 g of
purified water and dissolved to prepare an aqueous phase, and the
oil phase and the aqueous phase were then mixed together to obtain
an emulsion composition, which was used as an emulsion composition
according to Example 23.
[1-24] Preparation of Emulsion Composition According to Example
24
[0172] An oil phase was prepared by adding 32 g of 10%
Haematococcus algae pigment oil, 20 g of lutein/zeaxanthin oil,
16.8 g of triglyceride, 2 g of mix tocopherol, and 5 g of
decaglycerin monolaurate, and mixing and dissolving the resultant.
Subsequently, 10 g of sucrose laurate having an HLB value of 16, 6
g of propylene glycol, and 3 g of glycerin were added to 5.2 g of
purified water and dissolved to prepare an aqueous phase, and the
oil phase and the aqueous phase were then mixed together to obtain
an emulsion composition, which was used as an emulsion composition
according to Example 24. Table 4 shows the formulations of the
above emulsion compositions according to Examples 20 to 24.
TABLE-US-00004 TABLE 4 Example 20 Example 21 Example 22 Example 23
Example 24 Raw material Weight Weight Weight Weight Weight 20%
Haematococcus algae pigment oil -- -- -- -- -- (AstaReal Oil 200SS
(astaxanthins content: 20.3%, carotenoids content, excluding
astaxanthins: 3.2%, acyl glycerin content: 59.5%)) 10%
Haematococcus algae pigment oil 32 32 32 32 32 (AstaReal L10
(astaxanthins content: 11.3%, carotenoids content, excluding
astaxanthins: 7.5%, of acyl glycerin content: 70.2%))
Lutein/zeaxanthin 20 20 20 20 20 (Lutemax 2020 (produced by
OmniActive Health Technologies)) Medium chain fatty acid
triglyceride 6.8 10.8 14.8 11.8 16.8 Mix tocopherol 2 2 2 2 2
Lecithin paste (lecithin content: 60% or more) -- -- -- -- --
Tetraglycerin monooleate -- -- -- -- -- (SY-Glyster FMO-3S
(produced by Sakamoto Yakuhin Kogyo Co., Ltd.)) Decaglycerin
monolaurate 15 15 15 10 5 (NIKKOL DECAGLYN 1-L (produced by Nikko
Chemicals Co., Ltd.)) Sucrose stearate (HLB19) -- -- -- -- -- (DK
ESTER SS (produced by DKS Co. Ltd.)) Sucrose stearate (HLB5) (RYOTO
Sugar Ester S-570 (produced by -- -- -- -- -- Mitsubishi-Kagaku
Foods Corp.)) Sucrose laurate (HLB16) ("RYOTO Sugar Ester L-1695
(produced by 10 6 2 10 10 Mitsubishi-Kagaku Foods Corp.)) Sucrose
laurate (HLB1) "RYOTO Sugar Ester L-195 (produced by -- -- -- -- --
Mitsubishi-Kagaku Foods Corp.)) Purified water 5.2 5.2 5.2 5.2 5.2
Ethanol -- -- -- -- -- Propylene glycol 6 6 6 6 6 Glycerin 3 3 3 3
3 Total (g) 100 100 100 100 100
[1-25] Preparation of Emulsion Composition According to Example
25
[0173] An oil phase was prepared by adding 32 g of 10%
Haematococcus algae pigment oil, 20 g of lutein/zeaxanthin oil,
21.8 g of triglyceride, and 2 g of mix tocopherol, and mixing and
dissolving the resultant. Subsequently, 5 g of sucrose stearate
having an HLB value of 19, 5 g of sucrose laurate having an HLB
value of 16, 6 g of propylene glycol, and 3 g of glycerin were
added to 5.2 g of purified water and dissolved to prepare an
aqueous phase, and the oil phase and the aqueous phase were then
mixed together to obtain an emulsion composition, which was used as
an emulsion composition according to Example 25.
[1-26] Preparation of Emulsion Composition According to Example
26
[0174] An oil phase was prepared by adding 32 g of 10%
Haematococcus algae pigment oil, 20 g of lutein/zeaxanthin oil,
11.8 g of triglyceride, 2 g of mix tocopherol, and 10.0 g of
sucrose laurate having an HLB value of 1, and mixing and dissolving
the resultant. Subsequently, 10.0 g of sucrose stearate having an
HLB value of 19, 6 g of propylene glycol, and 3 g of glycerin were
added to 5.2 g of purified water and dissolved to prepare an
aqueous phase, and the oil phase and the aqueous phase were then
mixed together to obtain an emulsion composition, which was used as
an emulsion composition according to Example 26.
[1-27] Preparation of Emulsion Composition According to Example
27
[0175] An oil phase was prepared by adding 32 g of 10%
Haematococcus algae pigment oil, 20 g of lutein/zeaxanthin oil,
11.8 g of triglyceride, 2 g of mix tocopherol, and 10.0 g of
sucrose stearate having an HLB value of 5, and mixing and
dissolving the resultant. Subsequently, 10 g of sucrose laurate
having an HLB value of 16, 6 g of propylene glycol, and 3 g of
glycerin were added to 5.2 g of purified water and dissolved to
prepare an aqueous phase, and the oil phase and the aqueous phase
were then mixed together to obtain an emulsion composition, which
was used as an emulsion composition according to Example 27. Table
5 shows the formulations of the above emulsion compositions
according to Examples 25 to 27.
TABLE-US-00005 TABLE 5 Example 25 Example 26 Example 27 Raw
material Weight Weight Weight 20% Haematococcus algae pigment oil
-- -- -- (AstaReal Oil 200SS (astaxanthins content: 20.3%,
carotenoids content, excluding astaxanthins: 3.2%, acyl glycerin
content: 59.5%)) 10% Haematococcus algae pigment oil 32 32 32
(AstaReal L10 (astaxanthins content: 11.3%, carotenoids content,
excluding astaxanthins: 7.5%, of acyl glycerin content: 70.2%))
Lutein/zeaxanthin 20 20 20 (Lutemax 2020 (produced by OmniActive
Health Technologies)) Medium chain fatty acid triglyceride 21.8
11.8 11.8 Mix tocopherol 2 2 2 Lecithin paste (lecithin content:
60% or more) -- -- -- Tetraglycerin monooleate -- -- -- (SY-Glyster
FMO-3S (produced by Sakamoto Yakuhin Kogyo Co., Ltd.)) Decaglycerin
monolaurate -- -- -- (NIKKOL DECAGLYN 1-L (produced by Nikko
Chemicals Co., Ltd.)) Sucrose stearate (HLB19) 5 10 -- (DK ESTER SS
(produced by DKS Co. Ltd.)) Sucrose stearate (HLB5) (RYOTO Sugar
Ester S-570 (produced by -- -- 10 Mitsubishi-Kagaku Foods Corp.))
Sucrose laurate (HLB16) ("RYOTO Sugar Ester L-1695 (produced by 5
-- 10 Mitsubishi-Kagaku Foods Corp.)) Sucrose laurate (HLB1) "RYOTO
Sugar Ester L-195 (produced by -- 10 -- Mitsubishi-Kagaku Foods
Corp.)) Purified water 5.2 5.2 5.2 Ethanol -- -- -- Propylene
glycol 6 6 6 Glycerin 3 3 3 Total (g) 100 100 100
[1-28] Preparation of Emulsion Composition According to Example
28
[0176] An oil phase was prepared by adding 32 g of 10%
Haematococcus algae pigment oil, 20 g of lutein/zeaxanthin oil, 6.8
g of triglyceride, 2 g of mix tocopherol, and 15 g of decaglycerin
monolaurate, and mixing and dissolving the resultant. Subsequently,
10 g of sucrose stearate having an HLB value of 19, 6 g of
propylene glycol, and 3 g of glycerin were added to 5.2 g of
purified water and dissolved to prepare an aqueous phase, and the
oil phase and the aqueous phase were then mixed together to obtain
an emulsion composition, which was used as an emulsion composition
according to Example 28.
[1-29] Preparation of Emulsion Composition According to Example
29
[0177] An oil phase was prepared by adding 32 g of 10%
Haematococcus algae pigment oil, 20 g of lutein/zeaxanthin oil,
10.8 g of triglyceride, 2 g of mix tocopherol, and 15 g of
decaglycerin monolaurate, and mixing and dissolving the resultant.
Subsequently, 6 g of sucrose stearate having an HLB value of 19, 6
g of propylene glycol, and 3 g of glycerin were added to 5.2 g of
purified water and dissolved to prepare an aqueous phase, and the
oil phase and the aqueous phase were then mixed together to obtain
an emulsion composition, which was used as an emulsion composition
according to Example 29.
[1-30] Preparation of Emulsion Composition According to Example
30
[0178] An oil phase was prepared by adding 32 g of 10%
Haematococcus algae pigment oil, 20 g of lutein/zeaxanthin oil,
14.8 g of triglyceride, 2 g of mix tocopherol, and 15 g of
decaglycerin monolaurate, and mixing and dissolving the resultant.
Subsequently, 2 g of sucrose stearate having an HLB value of 19, 6
g of propylene glycol, and 3 g of glycerin were added to 5.2 g of
purified water and dissolved to prepare an aqueous phase, and the
oil phase and the aqueous phase were then mixed together to obtain
an emulsion composition, which was used as an emulsion composition
according to Example 30.
[1-31] Preparation of Emulsion Composition According to Example
31
[0179] An oil phase was prepared by adding 32 g of 10%
Haematococcus algae pigment oil, 20 g of lutein/zeaxanthin oil,
11.8 g of triglyceride, 2 g of mix tocopherol, and 10 g of
decaglycerin monolaurate, and mixing and dissolving the resultant.
Subsequently, 10 g of sucrose stearate having an HLB value of 19, 6
g of propylene glycol, and 3 g of glycerin were added to 5.2 g of
purified water and dissolved to prepare an aqueous phase, and the
oil phase and the aqueous phase were then mixed together to obtain
an emulsion composition, which was used as an emulsion composition
according to Example 31.
[1-32] Preparation of Emulsion Composition According to Example
32
[0180] An oil phase was prepared by adding 32 g of 10%
Haematococcus algae pigment oil, 20 g of lutein/zeaxanthin oil,
16.8 g of triglyceride, 2 g of mix tocopherol, and 5 g of
decaglycerin monolaurate, and mixing and dissolving the resultant.
Subsequently, 10 g of sucrose stearate having an HLB value of 19, 6
g of propylene glycol, and 3 g of glycerin were added to 5.2 g of
purified water and dissolved to prepare an aqueous phase, and the
oil phase and the aqueous phase were then mixed together to obtain
an emulsion composition, which was used as an emulsion composition
according to Example 32. Table 6 shows the formulations of the
above emulsion compositions according to Examples 28 to 32.
TABLE-US-00006 TABLE 6 Example 28 Example 29 Example 30 Example 31
Example 32 Raw material Weight Weight Weight Weight Weight 20%
Haematococcus algae pigment oil -- -- -- -- -- (AstaReal Oil 200SS
(astaxanthins content: 20.3%, carotenoids content, excluding
astaxanthins: 3.2%, acyl glycerin content: 59.5%)) 10%
Haematococcus algae pigment oil 32 32 32 32 32 (AstaReal L10
(astaxanthins content: 11.3%, carotenoids content, excluding
astaxanthins: 7.5%, of acyl glycerin content: 70.2%))
Lutein/zeaxanthin 20 20 20 20 20 (Lutemax 2020 (produced by
OmniActive Health Technologies)) Medium chain fatty acid
triglyceride 6.8 10.8 14.8 11.8 16.8 Mix tocopherol 2 2 2 2 2
Lecithin paste (lecithin content: 60% or more) -- -- -- -- --
Tetraglycerin monooleate -- -- -- -- -- (SY-Glyster FMO-3S
(produced by Sakamoto Yakuhin Kogyo Co., Ltd.)) Decaglycerin
monolaurate 15 15 15 10 5 (NIKKOL DECAGLYN 1-L (produced by Nikko
Chemicals Co., Ltd.)) Sucrose stearate (HLB19) 10 6 2 10 10 (DK
ESTER SS (produced by DKS Co. Ltd.)) Sucrose stearate (HLB5) (RYOTO
Sugar Ester S-570 (produced by -- -- -- -- -- Mitsubishi-Kagaku
Foods Corp.)) Sucrose laurate (HLB16) ("RYOTO Sugar Ester L-1695
(produced by -- -- -- -- -- Mitsubishi-Kagaku Foods Corp.)) Sucrose
laurate (HLB1) "RYOTO Sugar Ester L-195 (produced by -- -- -- -- --
Mitsubishi-Kagaku Foods Corp.)) Purified water 5.2 5.2 5.2 5.2 5.2
Ethanol -- -- -- -- -- Propylene glycol 6 6 6 6 6 Glycerin 3 3 3 3
3 Total (g) 100 100 100 100 100
[1-33] Preparation of Emulsion Composition According to Example
33
[0181] An oil phase was prepared by adding 21.5 g of 20%
Haematococcus algae pigment oil, 37.5 g of triglyceride, 2 g of mix
tocopherol, 20 g of tetraglycerin monooleate, 6 g of decaglycerin
monolaurate, and 0.4 g of ethanol, and mixing and dissolving the
resultant. Subsequently, 1.52 g of sucrose laurate and 9 g of
glycerin were added to 2.08 g of purified water and dissolved to
prepare an aqueous phase, and the oil phase and the aqueous phase
were then mixed together to obtain an emulsion composition, which
was used as an emulsion composition according to Example 33.
[1-34] Preparation of Emulsion Composition According to Example
34
[0182] An oil phase was prepared by adding 43 g of 10%
Haematococcus algae pigment oil, 12 g of triglyceride, 2 g of mix
tocopherol, 18 g of tetraglycerin monooleate, and 1 g of ethanol,
and mixing and dissolving the resultant. Subsequently, 6 g of
sucrose stearate having an HLB value of 19, 3.8 g of sucrose
laurate having an HLB value of 16, and 9 g of glycerin were added
to 5.2 g of purified water and dissolved to prepare an aqueous
phase, and the oil phase and the aqueous phase were then mixed
together to obtain an emulsion composition, which was used as an
emulsion composition according to Example 34.
[1-35] Preparation of Emulsion Composition According to Example
35
[0183] An oil phase was prepared by adding 43 g of 10%
Haematococcus algae pigment oil, 11.8 g of triglyceride, 2 g of mix
tocopherol, 18 g of tetraglycerin monooleate, 3 g of decaglycerin
monolaurate, and 1 g of ethanol, and mixing and dissolving the
resultant. Subsequently, 7 g of sucrose stearate having an HLB
value of 19 and 9 g of glycerin were added to 5.2 g of purified
water and dissolved to prepare an aqueous phase, and the oil phase
and the aqueous phase were then mixed together to obtain an
emulsion composition, which was used as an emulsion composition
according to Example 35. Table 7 shows the formulations of the
above emulsion compositions according to Examples 33 to 35.
TABLE-US-00007 TABLE 7 Example 33 Example 34 Example 35 Raw
material Weight Weight Weight 20% Haematococcus algae pigment oil
21.5 -- -- (AstaReal Oil 200SS (astaxanthins content: 20.3%,
carotenoids content, excluding astaxanthins: 3.2%, acyl glycerin
content: 59.5%)) 10% Haematococcus algae pigment oil -- 43 43
(AstaReal L10 (astaxanthins content: 11.3%, carotenoids content,
excluding astaxanthins: 7.5%, of acyl glycerin content: 70.2%))
Lutein/zeaxanthin -- -- -- (Lutemax 2020 (produced by OmniActive
Health Technologies)) Medium chain fatty acid triglyceride 37.5 12
11.8 Mix tocopherol 2 2 2 Lecithin paste (lecithin content: 60% or
more) -- -- -- Tetraglycerin monooleate 20 18 18 (SY-Glyster FMO-3S
(produced by Sakamoto Yakuhin Kogyo Co., Ltd.)) Decaglycerin
monolaurate 6 -- 3 (NIKKOL DECAGLYN 1-L (produced by Nikko
Chemicals Co., Ltd.)) Sucrose stearate (HLB19) -- 6 7 (DK ESTER SS
(produced by DKS Co. Ltd.)) Sucrose stearate (HLB5) (RYOTO Sugar
Ester S-570 (produced by -- -- -- Mitsubishi-Kagaku Foods Corp.))
Sucrose laurate (HLB16) ("RYOTO Sugar Ester L-1695 (produced by
1.52 3.8 -- Mitsubishi-Kagaku Foods Corp.)) Sucrose laurate (HLB1)
"RYOTO Sugar Ester L-195 (produced by -- -- -- Mitsubishi-Kagaku
Foods Corp.)) Purified water 2.08 5.2 5.2 Ethanol 0.4 1 1 Propylene
glycol -- -- -- Glycerin 9 9 9 Total (g) 100 100 100
[1-36] Preparation of Emulsion Composition According to Example
36
[0184] An oil phase was prepared by adding 21.5 g of 20%
Haematococcus algae pigment oil, 33.5 g of triglyceride, 2 g of mix
tocopherol, 15 g of tetraglycerin monooleate, and 3 g of
decaglycerin monolaurate, and mixing and dissolving the resultant.
Subsequently, 6 g of sucrose stearate having an HLB value of 19,
3.8 g of sucrose laurate having an HLB value of 16, and 9 g of
glycerin were added to 5.2 g of purified water and dissolved to
prepare an aqueous phase, and the oil phase, the aqueous phase, and
1 g of ethanol were then mixed together to obtain an emulsion
composition, which was used as an emulsion composition according to
Example 36.
[1-37] Preparation of Emulsion Composition According to Example
37
[0185] An oil phase was prepared by adding 43 g of 10%
Haematococcus algae pigment oil, 12 g of triglyceride, 2 g of mix
tocopherol, 15 g of tetraglycerin monooleate, and 4.5 g of
decaglycerin monolaurate, and mixing and dissolving the resultant.
Subsequently, 4.5 g of sucrose stearate having an HLB value of 19,
3.8 g of sucrose laurate having an HLB value of 16, and 9 g of
glycerin were added to 5.2 g of purified water and dissolved to
prepare an aqueous phase, and the oil phase, the aqueous phase, and
1 g of ethanol were then mixed together to obtain an emulsion
composition, which was used as an emulsion composition according to
Example 37.
[1-38] Preparation of Emulsion Composition According to Example
38
[0186] An oil phase was prepared by adding 43 g of 10%
Haematococcus algae pigment oil, 12 g of triglyceride, 2 g of mix
tocopherol, 15 g of tetraglycerin monooleate, and 6 g of
decaglycerin monolaurate, and mixing and dissolving the resultant.
Subsequently, 3 g of sucrose stearate having an HLB value of 19,
3.8 g of sucrose laurate having an HLB value of 16, and 9 g of
glycerin were added to 5.2 g of purified water and dissolved to
prepare an aqueous phase, and the oil phase, the aqueous phase, and
1 g of ethanol were then mixed together to obtain an emulsion
composition, which was used as an emulsion composition according to
Example 38.
[1-39] Preparation of Emulsion Composition According to Example
39
[0187] An oil phase was prepared by adding 43 g of 10%
Haematococcus algae pigment oil, 12 g of triglyceride, 2 g of mix
tocopherol, 16 g of tetraglycerin monooleate, and 2 g of
decaglycerin monolaurate, and mixing and dissolving the resultant.
Subsequently, 6 g of sucrose stearate having an HLB value of 19,
3.8 g of sucrose laurate having an HLB value of 16, and 9 g of
glycerin were added to 5.2 g of purified water and dissolved to
prepare an aqueous phase, and the oil phase, the aqueous phase, and
1 g of ethanol were then mixed together to obtain an emulsion
composition, which was used as an emulsion composition according to
Example 39.
[1-40] Preparation of Emulsion Composition According to Example
40
[0188] An oil phase was prepared by adding 43 g of 10%
Haematococcus algae pigment oil, 12 g of triglyceride, 2 g of mix
tocopherol, 17.5 g of tetraglycerin monooleate, and 0.5 g of
decaglycerin monolaurate, and mixing and dissolving the resultant.
Subsequently, 6 g of sucrose stearate having an HLB value of 19,
3.8 g of sucrose laurate having an HLB value of 16, and 9 g of
glycerin were added to 5.2 g of purified water and dissolved to
prepare an aqueous phase, and the oil phase, the aqueous phase, and
1 g of ethanol were then mixed together to obtain an emulsion
composition, which was used as an emulsion composition according to
Example 40.
[1-41] Preparation of Emulsion Composition According to Example
41
[0189] An oil phase was prepared by adding 21.5 g of
lutein/zeaxanthin, 33.5 g of triglyceride, 2 g of mix tocopherol,
15 g of tetraglycerin monooleate, and 3 g of decaglycerin
monolaurate, and mixing and dissolving the resultant. Subsequently,
6 g of sucrose stearate having an HLB value of 19, 3.8 g of sucrose
laurate having an HLB value of 16, and 9 g of glycerin were added
to 5.2 g of purified water and dissolved to prepare an aqueous
phase, and the oil phase, the aqueous phase, and 1 g of ethanol
were then mixed together to obtain an emulsion composition, which
was used as an emulsion composition according to Example 41.
[1-42] Preparation of Emulsion Composition According to Example
42
[0190] An oil phase was prepared by adding 21.5 g of 20%
Haematococcus algae pigment oil, 21.5 g of lutein/zeaxanthin, 12 g
of triglyceride, 2 g of mix tocopherol, 15 g of tetraglycerin
monooleate, and 3 g of decaglycerin monolaurate, and mixing and
dissolving the resultant. Subsequently, 6 g of sucrose stearate
having an HLB value of 19, 3.8 g of sucrose laurate having an HLB
value of 16, and 9 g of glycerin were added to 5.2 g of purified
water and dissolved to prepare an aqueous phase, and the oil phase,
the aqueous phase, and 1 g of ethanol were then mixed together to
obtain an emulsion composition, which was used as an emulsion
composition according to Example 42. Table 8 shows the formulations
of the above emulsion compositions according to Examples 36 to
42.
TABLE-US-00008 TABLE 8 Exam- Exam- Exam- Exam- Exam- Exam- Exam-
ple 36 ple 37 ple 38 ple 39 ple 40 ple 41 ple 42 Raw material
Weight Weight Weight Weight Weight Weight Weight 20% Haematococcus
algae pigment oil 21.5 -- -- -- -- -- 21.5 (AstaReal Oil 200SS
(astaxanthins content: 20.3%, carotenoids content, excluding
astaxanthins: 3.2%, acyl glycerin content: 59.5%)) 10%
Haematococcus algae pigment oil 43 43 43 43 -- -- (AstaReal L10
(astaxanthins content: 11.3%, carotenoids content, excluding
astaxanthins: 7.5%, of acyl glycerin content: 70.2%))
Lutein/zeaxanthin -- -- -- -- -- 21.5 21.5 (Lutemax 2020 (produced
hy OmniActive Health Technologies)) Medium chain fatty acid
triglyceride 33.5 12 12 12 12 33.5 12 Mix tocopherol 2 2 2 2 2 2 2
Lecithin paste (lecithin content: 60% or more) -- -- -- -- -- -- --
Tetraglycerin monooleate 15 15 15 16 17.5 15 15 (SY-Glyster FMO-3S
(produced by Sakamoto Yakuhin Kogyo Co., Ltd.)) Decaglycerin
monolaurate 3 4.5 6 2 0.5 3 3 (NIKKOL DECAGLYN 1-L (produced by
Nikko Chemicals Co., Ltd.)) Sucrose stearate (HLB19) 6 4.5 3 6 6 6
6 (DK ESTER SS (produced by DKS Co. Ltd.)) Sucrose stearate (HLB5)
(RYOTO Sugar Ester S-570 (produced by -- -- -- -- -- -- --
Mitsubishi-Kagaku Foods Corp.)) Sucrose laurate (HLB16) ("RYOTO
Sugar Ester L-1695 (produced by 3.8 3.8 3.8 3.8 3.8 3.8 3.8
Mitsubishi-Kagaku Foods Corp.)) Sucrose laurate (HLB1) "RYOTO Sugar
Ester L-195 (produced by -- -- -- -- -- -- -- Mitsubishi-Kagaku
Foods Corp.)) Purified water 5.2 5.2 5.2 5.2 5.2 5.2 5.2 Ethanol 1
1 1 1 1 1 1 Propylene glycol -- -- -- -- -- -- -- Glycerin 9 9 9 9
9 9 9 Total (g) 100 100 100 100 100 100 100
2. Preparation of Comparative Compositions
[0191] Next, comparative compositions 1 to 4 were prepared as
described below. In preparation of comparative compositions 1 to 4,
"AstaReal Oil 200SS (produced by AstaReal Co., Ltd.)" was used as
"20% Haematococcus algae pigment oil, "AstaReal L10 (produced by
AstaReal Co., Ltd.)" was used as "10% Haematococcus algae pigment
oil", and "Lutemax 2020 (produced by OmniActive Health
Technologies)" was used as "lutein/zeaxanthin".
[0192] Used as comparative compositions 1, 2, and 3, were 20%
Haematococcus algae pigment oil, 10% Haematococcus algae pigment
oil, and lutein/zeaxanthin oil, respectively. Comparative
composition 4 was prepared by mixing 62 g of 10% Haematococcus
algae pigment oil and 38 g of lutein/zeaxanthin oil. Table 9 shows
the formulations of comparative compositions 1 to 4.
TABLE-US-00009 TABLE 9 Comparative Comparative Comparative
composition 1 Comparative composition 3 composition 4 Raw material
Weight composition 2 Weight Weight 20% Haematococcus algae pigment
oil 100 -- -- -- (AstaReal Oil 200SS (astaxanthins content: 20.3%,
carotenoids content, excluding astaxanthins: 3.2%, acyl glycerin
content: 59.5%)) 10% Haematococcus algae pigment oil -- 100 -- 62
(AstaReal L10 (astaxanthins content: 11.3%, carotenoids content,
excluding astaxanthins: 7.5%, of acyl glycerin content: 70.2%))
Lutein/zeaxanthin -- -- 100 38 (Lutemax 2020 (produced by
OmniActive Health Technologies)) Total (g) 100 100 100 100
3. Evaluation of Affinity with Soft Capsule Shell
[0193] Affinity with a soft capsule shell was evaluated for the
emulsion compositions according to Examples 1 to 42 through the
following procedure.
[0194] A plant-based coated MCT soft capsule was precipitated in
each of the emulsion compositions according to Examples 1 to 42 and
left to stand at room temperature for 2 days, and thereafter the
soft capsule was taken out. The shell of each soft capsule was
checked for deformation and softening, and when no deformation,
depression, or softening of the soft capsule shell occurred, the
emulsion composition was considered to have low affinity with the
soft capsule shell (.largecircle.), and when deformation,
depression, or softening of the soft capsule shell occurred, the
emulsion composition was considered to have high affinity with the
soft capsule shell (x). FIG. 1 shows the results.
[0195] As demonstrated in FIG. 1, the deformation, depression, or
softening of the soft capsule shell did not occur for all the
emulsion compositions according to Examples 1 to 42, indicating low
affinity with the soft capsule shell (.largecircle.), and this
result revealed that the emulsion composition according to the
present invention can be formulated into a soft capsule
formulation.
4. Systemic Absorption Test
[0196] The emulsion compositions according to Examples 1 to 42 and
comparative compositions 1 to 4 prepared were each subjected to a
systemic absorption test for carotenoids through the following
procedure.
[3-1] Preparation of Samples
[0197] To Wistar rats fasted overnight (male, 4 to 6 animals per
group, body weight: 200 to 250 g, 8- to 10-week-old), the emulsion
compositions according to Examples 1 to 42 and comparative
compositions 1 to 4 were administered with a feeding needle. At the
administration, the emulsion compositions according to Examples 1
to 42 and comparative compositions 1 to 4 were each diluted with
medium chain fatty acid triglyceride to prepare for administration
of 4.4 cc/kg rat weight, so that when the composition to be
administered contained only astaxanthin as a carotenoid, the dose
of astaxanthin (in terms of the free form) reached 100 mg/kg rat
weight, when the composition to be administered contained only
lutein/zeaxanthin, the dose of lutein reached 100 mg/kg rat weight
and the dose of zeaxanthin reached 20 mg/kg rat weight, and when
the composition to be administered contained astaxanthin and
lutein/zeaxanthin, the dose of astaxanthin (in terms of the free
form) reached 100 mg/kg rat weight and the dose of lutein reached
120 mg/kg rat weight and the dose of zeaxanthin reached 25 mg/kg
rat weight. After the administration, and 3, 6, 9, and 24 hours
after the administration, blood was collected from the jugular
vein, and the plasma was separated. The plasma obtained was stored
at -80.degree. C. before quantitative analysis of carotenoids.
[0198] To 100 .mu.L of each plasma sample obtained, 500 .mu.L of
ethanol solution of butylated hydroxytoluene (BHT; 50 .mu.g/mL) and
100 .mu.L of 100 ng/mL acetone solution of an internal standard
(trans-.beta.-apo-8T-carotenal, 10829; produced by Sigma-Aldrich
Co. LLC) were added, the sample was vigorously stirred by using a
vortex mixer for 15 seconds, 5 mL of hexane was then added thereto,
and the sample was further vigorously stirred by using a vortex
mixer for 15 seconds. This stirring process was performed three
times, and centrifugation was then performed at a rotational
frequency of 3500 rpm for 10 minutes. After the centrifugation, 4
mL of the resulting supernatant was collected, and filtered through
a membrane filter with a mesh size of 0.45 .mu.m. The resulting
filtrate was concentrated with a centrifugal evaporator, and then
redissolved in 150 .mu.L of acetone to obtain a sample, which was
subjected to reverse-phase HPLC.
[0199] Carotenoid standard solutions were prepared as follows: 1 mL
of 2 .mu.g/mL acetone solution of astaxanthin standard reagent
(460-031-M250; Astaxanthin, produced by Alexis Biochemicals) and
2.5 mL of 800 ng/mL acetone solution of an internal standard
(trans-.beta.-apo-8T-carotenal, 10829; produced by Sigma-Aldrich
Co. LLC) were mixed, and the resulting solution was diluted with
acetone to a volume of 20.0 mL in a graduated cylinder to prepare
an astaxanthin standard solution; 2 mL of 2.67 .mu.g/mL acetone
solution of lutein standard and 2.5 mL of 800 ng/mL acetone
solution of an internal standard (trans-.beta.-apo-8T-carotenal,
10829; produced by Sigma-Aldrich Co. LLC) were mixed, and the
resulting solution was diluted with acetone to a volume of 20.0 mL
in a graduated cylinder to prepare a lutein standard solution; and
2 mL of 1.55 .mu.g/mL acetone solution of zeaxanthin standard
reagent and 2.5 mL of 800 ng/mL acetone solution of an internal
standard (trans-.beta.-apo-8T-carotenal, 10829; produced by
Sigma-Aldrich Co. LLC) were mixed, and the resulting solution was
diluted with acetone to a volume of 20.0 mL in a graduated cylinder
to prepare a zeaxanthin standard solution. The standard solutions
prepared were subjected to reverse-phase HPLC in the same manner,
and astaxanthin, lutein, and zeaxanthin concentrations were
determined through comparison of peak area ratios acquired.
[3-2] HPLC Conditions
[0200] HPLC was performed by using a Shimadzu LC20A Series (pump:
LC-20AD, degasser: DGU-20A5R, autosampler: SIL-20AC, column oven:
CTO-20AC, detector: SPD-20AV, system controller: CBM-20A) and a
YMC-Carotenoid (4.6.times.250 mm, particle size: 5 .mu.m) as an
analysis column. For the mobile phase, solution A (methanol),
solution B (tert-butyl methyl ether), and solution C (1% (v/v)
aqueous solution of phosphoric acid) were used. Gradient elution
was performed in the following manner: the mixing ratio between
solution A and solution B was 81:13 (% ratio) at initiation; the
ratio of solution B reached 28% after the lapse of 15 minutes, and
78% after the lapse of 27 minutes; the composition with the mixing
ratio of solution B being 78% was retained until the lapse of 31
minutes; thereafter the mixing ratio was returned to that at
initiation after the lapse of 31.01 minutes; and elution was
performed at the composition at initiation until the lapse of 40
minutes. The mixing ratio of solution C in the composition was
always retained at 6%. The temperature of the column oven was set
to 25.degree. C., and the detection wavelength of the UV/VIS
detector was set to 470 nm for measurement, and the flow rate was 1
mL/min.
[0201] Calculated was area under the blood concentration-time curve
after 0 to 24 hours (AUC.sub.0-24hr; hereinafter, abbreviated as
"AUC") for each of astaxanthin, lutein, and zeaxanthin in the
systemic absorption test conducted for the emulsion compositions
according to Examples 1 to 42 and comparative compositions 1 to 4.
AUC ratios of the emulsion compositions according to Examples 1 to
42 to comparative compositions 1 to 4 were calculated by using the
following expression, and FIG. 2 shows the results.
[0202] AUC Ratio=AUC value of any of emulsion compositions
according to Examples 1 to 42/AUC value of corresponding
composition among comparative compositions 1 to 4
[0203] As shown in FIG. 2, the AUC ratios of the emulsion
compositions according to Examples 1 to 40 and 42 to the
corresponding comparative composition for astaxanthin were 2.7,
1.5, 2.4, 1.7, 1.5, 1.3, 1.9, 1.2, 1.9, 1.2, 2.3, 1.1, 1.2, 2.0,
1.3, 1.8, 1.2, 1.1, 1.5, 1.6, 1.9, 1.4, 2.1, 1.7, 1.3, 1.2, 1.6,
2.1, 1.8, 1.4, 2.2, 2.1, 1.8, 4.6, 2.0, 1.5, 2.6, 1.8, 2.6, 2.2,
and 1.8, respectively. The AUC ratios of the emulsion compositions
according to Examples 2 to 10, 12 to 15, 17 to 32, 41, and 42 to
the corresponding comparative composition for lutein were 1.4, 1.7,
1.3, 1.6, 1.2, 1.3, 1.3, 1.4, 1.2, 1.0, 1.1, 1.3, 1.1, 1.4, 1.5,
1.0, 1.1, 1.4, 1.3, 1.7, 1.3, 1.3, 0.9, 1.2, 1.2, 1.1, 1.0, 1.2,
1.2, 1.3, and 1.3, respectively. The AUC ratios of the emulsion
compositions according to Examples 2 to 10, 12 to 15, 17 to 32, 41,
and 42 to the corresponding comparative composition for zeaxanthin
were 2.5, 10.1, 9.6, 10.8, 2.8, 4.1, 3.3, 4.7, 3.7, 3.6, 5.4, 3.6,
4.9, 1.4, 1.9, 0.6, 2.0, 4.0, 3.4, 3.7, 5.0, 5.5, 2.6, 2.5, 1.4,
0.8, 0.8, 1.9, 1.5, 13.3, and 1.8.
[0204] From these results, showing that at least any value of the
AUC ratios of each of the emulsion compositions according to
Examples 1 to 42 and the corresponding comparative composition for
astaxanthin, lutein, and zeaxanthin was 1.4 or higher (among the
AUC ratios of each of the emulsion compositions according to
Examples 1 to 42 to the corresponding comparative composition for
astaxanthin, lutein, and zeaxanthin, the highest value was 1.4 or
higher), the emulsion composition according to the present
invention was revealed to allow higher systemic absorption for
carotenoids than conventional emulsion compositions.
5. Evaluation of Homogeneity
[0205] Homogeneity was evaluated for the emulsion compositions
according to Examples 11, 34, and 36 through the following
procedure.
[0206] The emulsion compositions according to Examples 11, 34, and
36 with the loading of ethanol set to 0 g (0% by weight), 0.1 g
(0.1% by weight), 0.25 g (0.25% by weight), 0.5 g (0.5% by weight),
0.75 g (0.75% by weight), or 1 g (1% by weight) were prepared,
where the total amount was adjusted with the loading of
triglyceride. The emulsion composition according to Example 36 was
prepared with addition of a dihydric alcohol such as propylene
glycol or a (polyhydric) sugar alcohol such as xylitol, sorbitol,
lactitol, and erythritol in place of ethanol (monohydric alcohol).
Each of the emulsion compositions prepared were heated at
60.degree. C. for 20 minutes and then sieved through an 80-mesh
stainless steel test sieve, and the weight (g) of the test sieve
after sieving was measured. Subsequently, the weight (g) of the
test sieve before sieving was subtracted from the weight (g) of the
test sieve measured after sieving to calculate the weight (g) of
residues of each of the emulsion compositions according to Examples
11, 34, and 36 on the test sieve after sieving, and the weight of
residues on the test sieve after sieving was then divided by the
amount of the emulsion composition subjected to sieving to
calculate the residue proportion (% by weight) on the test sieve
after sieving. Then, when the calculated residue proportion (% by
weight) on the test sieve after sieving was lower than 10%, the
emulsion composition was considered to be highly homogeneous
(.largecircle.), and when the residue proportion was 10% or higher
and lower than 20%, the emulsion composition was considered to have
common homogeneity (.DELTA.), and when the residue proportion was
30% or higher, the emulsion composition was considered to be
inhomogeneous (x). FIGS. 3 to 6 show the formulations of the
emulsion compositions prepared and the evaluation results.
[0207] As shown in FIGS. 3 to 5, it was demonstrated that emulsion
compositions prepared without addition of ethanol were not
homogeneous, and emulsion compositions prepared with addition of
ethanol had homogeneity. In addition, it was demonstrated that
emulsion compositions prepared with ethanol in a loading of 0.5% by
weight or 0.75% by weight or more were highly homogeneous. As shown
in FIG. 6, it was demonstrated that emulsion compositions prepared
even with addition of propylene glycol (dihydric alcohol) or a
(polyhydric) sugar alcohol such as xylitol, sorbitol, lactitol, and
erythritol in place of ethanol (monohydric alcohol) had homogeneity
similar to those with addition of ethanol. These results revealed
that the emulsion composition according to the present invention
had homogeneity by virtue of inclusion of an alcohol.
5. Soft Capsule
[0208] A carotenoid-containing soft capsule is obtained in such a
manner that 55 g of any of the emulsion compositions produced in
Examples 1 to 42, 40 g of diglycerin laurate (RIKEMAL L-71-D;
produced by RIKEN VITAMIN CO., LTD.), and 5 g of
polyoxyethylenesorbitan fatty acid ester were mixed to a
homogeneous state, and a soft capsule is filled with the mixture by
using a filling machine.
* * * * *